Sample records for meningitis cerebrospinal fluid

  1. Penetration of spectinomycin into cerebrospinal fluid duirng experimental meningitis.

    PubMed Central

    Delgado, D G; Brau, C J; Avent, C K

    1980-01-01

    The concentration of spectinomycin in serum and cerebrospinal fluid was compared in rabbits with and without experimental pneumococcal meningitis. When injected intravenously, spectinomycin could not be detected in the cerebrospinal fluid of normal rabbits. In rabbits with meningeal inflammation, however, spectinomycin penetrated the blood-brain barrier and produced significant cerebrospinal fluid concentrations, equal to or well above spectinomycin minimal inhibitory concentrations for many bacterial species. PMID:6446261

  2. Cerebrospinal fluid investigations in tuberculous meningitis.

    PubMed

    Donald, P R; Schoeman, J F; Cotton, M F; van Zyl, L E

    1991-01-01

    The results of conventional cerebrospinal fluid (CSF) investigations (CSF cell count, protein and glucose concentrations and Pandy's test for CSF globulin) obtained on admission and sequentially from weekly follow-up lumbar punctures for 4 weeks were evaluated in 99 children (median age 28 months) with stage II (50 children) and stage III (49 children) tuberculous meningitis. On admission, six children (6%) had a CSF cell count greater than 500 x 10(6)/l and nine (9%) a polymorphonuclear predominance. A CSF protein less than 0.8 g/l was found in 17 children (18%) of 97 in whom CSF protein was evaluated. Globulin was either absent or present as a trace only in 26 children (27%). CSF glucose was less than 2.2 mmol/l in 58 cases (60%) and less than 2.5 mmol/l in 67 (69%). In 63 children weekly CSF specimens obtained for the 1st 4 weeks of therapy showed an uninterrupted decline in cell count in 23 (37%), a fluctuating downward trend in 27 (43%) and a fluctuating upward trend in 13 (21%). Sequential CSF protein values in 57 children showed an uninterrupted rise in three (5%), a fluctuating upward course in 19 (33%), an uninterrupted downward trend in seven (12%), and a fluctuating downward course in 28 (49%). Of the 61 children in whom sequential CSF glucose concentrations were available, 11 (18%) experienced fluctuating concentrations, values falling to less than 2.2 mmol/l after being greater than 2.2 mmol/l on admission or after having risen to greater than 2.2 mmol/l.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1719923

  3. Cerebrospinal fluid ferritin levels in screening for meningism.

    PubMed

    Campbell, D R; Skikne, B S; Cook, J D

    1986-12-01

    To evaluate the potential diagnostic value of the ferritin concentration in cerebrospinal fluid (CSF), measurements were performed with an immunoradiometric assay in 23 control patients and in 65 patients with various neurologic disorders. The geometric mean ferritin level of 3.5 micrograms/L in controls was approximately 10% of the level in normal serum with an upper cutoff level of 10 micrograms/L. Only modest elevations in CSF ferritin concentration were observed in patients with viral meningitis and in those with various non-infectious neurologic disorders. On the other hand, marked elevations ranging between 27 and 322 micrograms/L (geometric mean, 90 micrograms/L) were observed in patients with bacterial or fungal meningitis. Results of the study indicate that CSF ferritin levels are a valuable adjunct in the early evaluation of patients presenting with meningism. PMID:3778261

  4. Opsonic activity of cerebrospinal fluid in experimental cryptococcal meningitis.

    PubMed Central

    Hobbs, M M; Perfect, J R; Granger, D L; Durack, D T

    1990-01-01

    The role of antibody in protection against infection with Cryptococcus neoformans is undefined. In this paper we describe the development of opsonic activity in the cerebrospinal fluid (CSF) of rabbits in response to cryptococcal meningitis. The opsonin appeared to be immunoglobulin G (IgG); the activity was heat stable, copurified with the IgG fraction during protein A separation, and could be absorbed by encapsulated cryptococci. Immunosuppression with cyclosporine could be administered to prevent or allow in vivo deposition of IgG on the polysaccharide capsule of yeast in the CSF. Both early and late cyclosporine regimens resulted in prolonged, severe meningeal infections corresponding to the complete absence of in vitro opsonic activity in the CSF. While the production of opsonic antibody is part of the successful host response against C. neoformans in the central nervous system of rabbits, the presence of specific immunoglobulin by itself is insufficient for complete protection. Images PMID:2194960

  5. Evaluation of cerebrospinal fluid (CSF) C-reactive protein in the diagnosis of suspected meningitis.

    PubMed

    Shaltout, A; el-Shirbiny, A; Killander, J; Ragheb, A; el Heit, S A

    1986-03-01

    Cerebrospinal fluid C-reactive protein (CSF-CRP) was studied in 183 consecutive infants and children with suspected meningitis, using a nephelometric technique. Cerebrospinal fluid C-reactive protein was above an empirically chosen level of 1 mg/1 in seven of 19 children with culture-proven bacterial meningitis, in only one of 15 children with viral meningitis, and three of 139 children with no meningitis. All 10 children with partially treated meningitis had CSF-CRP levels below 1 mg/1. There was good correlation between CSF-CRP and total protein levels in children with bacterial meningitis (R value 0.4999 P less than 0.05). The test was not sensitive enough for early differentiation between bacterial and viral meningitis. The test also did not add extra information regarding aetiology in partially treated meningitis. PMID:2428290

  6. Recovery of Angiostrongylus cantonensis from cerebrospinal fluid of a child with eosinophilic meningitis.

    PubMed Central

    Kuberski, T; Bart, R D; Briley, J M; Rosen, L

    1979-01-01

    Viable Angiostrongylus cantonensis was recovered from the cerebrospinal fluid of a 17-month-old boy with eosinophilic meningitis. Neurological findings were minimal, and the child had an uneventful recovery. PMID:479360

  7. Bactericidal Activity against Cephalosporin-ResistantStreptococcus pneumoniaein Cerebrospinal Fluid of Children with Acute Bacterial Meningitis

    Microsoft Academic Search

    KEITH P. KLUGMAN; IAN R. FRIEDLAND; ANDJOHN S. BRADLEY

    There are reports of failure of extended-spectrum cephalosporin treatment in pneumococcal meningitis. On the basis of in vitro and animal experimental studies, the addition of vancomycin or rifampin to an extended- spectrum cephalosporin has been recommended for empiric treatment of these patients. Cerebrospinal fluid (CSF) was taken from 31 children with bacterial meningitis randomized to receive ceftriaxone alone (n 511),

  8. Adult pneumococcal meningitis presenting with normocellular cerebrospinal fluid: two case reports

    PubMed Central

    2013-01-01

    Introduction Normocellular bacterial meningitis is rarely observed in adult patients. We here report two cases of adult patients with pneumococcal meningitis with a normal cerebrospinal fluid leukocyte count and review eight other cases in the literature. Case presentation Case 1 was a 34-year-old Japanese woman with a history of splenectomy who presented with pyrexia, nausea, headache, and loss of hearing in her right ear. She was in a hypotensive state with no neck stiffness and had a normal mental status at the initial presentation. She became progressively disoriented during out-patient management. A cerebrospinal fluid examination showed a normal leukocyte count despite the presence of Streptococcus pneumoniae, which was detectable with Gram staining. She survived after prompt treatment, but her hearing loss remained. Case 2 was a 62-year-old Japanese man with a history of laryngeal cancer who was transferred to our emergency department after an acute onset of delirium and rapid progression to septic shock. As in Case 1, cerebrospinal fluid examination showed a normal leukocyte count despite the presence of S. pneumoniae, which was detectable with Gram staining. Within 1 hour of arrival, he developed hypotension and subsequent cardiopulmonary arrest, and resuscitation was unsuccessful. Conclusions These cases imply that a normal leukocyte count in the cerebrospinal fluid does not exclude the possibility of bacterial meningitis. Gram staining of cerebrospinal fluid and immediate administration of antibiotics should be performed in all patients with suspected bacterial meningitis. PMID:24378083

  9. Lipocalin 2 in cerebrospinal fluid as a marker of acute bacterial meningitis

    PubMed Central

    2014-01-01

    Background Early differential diagnosis between acute bacterial and viral meningitis is problematic. We aimed to investigate whether the detection of lipocalin 2, a protein of the acute innate immunity response, may be used as a marker for acute bacterial meningitis. Methods Transgenic mice expressing the human transferrin were infected by intraperitoneal route and were imaged. Cerebrospinal fluid (CSF) was sampled up to 48hours post- infection to measure lipocalin 2. We also tested a collection of 90 and 44 human CSF with confirmed acute bacterial or acute viral meningitis respectively. Results Lipocalin 2 was detected after 5 h in CSF during experimental infection in mice. Lipocalin 2 levels were significantly higher (p?meningitis (mean 125 pg/mL, range 106–145 pg/mL) than in patients with acute viral meningitis (mean 2 pg/mL, range 0–6 pg/mL) with a sensitivity of 81%, a specificity of 93%, a positive predictive value of 96% and a negative predictive value of 71% in diagnosing acute bacterial meningitis. Conclusions Increased levels of lipocalin 2 in cerebrospinal fluid may discriminate between acute bacterial and viral meningitis in patients with clinical syndrome of meningitis. PMID:24885531

  10. Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. An evaluation using /sup 111/In-DTPA ventriculography

    SciTech Connect

    Grossman, S.A.; Trump, D.L.; Chen, D.C.; Thompson, G.; Camargo, E.E.

    1982-11-01

    Cerebrospinal fluid flow dynamics were evaluated by /sup 111/In-diethylenetriamine pentaacetic acid (/sup 111/In-DTPA) ventriculography in 27 patients with neoplastic meningitis. Nineteen patients (70 percent) had evidence of cerebrospinal fluid flow disturbances. These occurred as ventricular outlet obstructions, abnormalities of flow in the spinal canal, or flow distrubances over the cortical convexities. Tumor histology, physical examination, cerebrospinal fluid analysis, myelograms, and computerized axial tomographic scans were not sufficient to predict cerebrospinal fluid flow patterns. These data indicate that cerebrospinal fluid flow abnormalities are common in patients with neoplastic meningitis and that /sup 111/In-DTPA cerebrospinal fluid flow imaging is useful in characterizing these abnormalities. This technique provides insight into the distribution of intraventricularly administered chemotherapy and may provide explanations for treatment failure and drug-induced neurotoxicity in patients with neoplastic meningitis.

  11. Penetration of ceftazidime into cerebrospinal fluid of patients with bacterial meningitis.

    PubMed Central

    Modai, J; Vittecoq, D; Decazes, J M; Wolff, M; Meulemans, A

    1983-01-01

    Four 2-g doses of ceftazidime were infused intravenously over 30 min at 8-h intervals, first between days 2 and 4 and again between days 11 and 20, in 11 patients with bacterial meningitis undergoing treatment with other antibiotics. Concentrations of ceftazidime in serum and cerebrospinal fluid samples obtained 120 or 180 min after dose 4 were measured by high-pressure liquid chromatography. Concentrations in cerebrospinal fluid ranged from 2 to 30 micrograms/ml, depending on the sampling time and the time elapsed since the onset of the disease. PMID:6354077

  12. Penetration of amoxicillin and potassium clavulanate into the cerebrospinal fluid of patients with inflamed meninges.

    PubMed Central

    Bakken, J S; Bruun, J N; Gaustad, P; Tasker, T C

    1986-01-01

    A single intravenous dose of 2.0 g of amoxicillin and 0.2 g of potassium clavulanate was given to patients with bacterial meningitis, and the pharmacokinetics of both drugs in the cerebrospinal fluid (CSF) and plasma were evaluated. Twenty-one patients aged 14 to 76 years were studied. Both amoxicillin and potassium clavulanate were detectable in the CSF as early as 1 h and reached peak concentrations by approximately 2 h. The highest mean CSF concentrations were 2.25 micrograms/ml for amoxicillin and 0.25 micrograms/ml for potassium clavulanate and were found in patients with moderately or severely inflamed meninges. The CSF penetration relative to plasma for amoxicillin and potassium clavulanate was 5.8 and 8.4%, respectively. These levels suggest that the amoxicillin-potassium clavulanate combination may be effective for the treatment of bacterial meningitis caused by beta-lactamase-producing pathogens. PMID:3777911

  13. Measurement of cytokine levels in cerebrospinal fluid over time in neonatal Enterococcal meningitis.

    PubMed

    Ikeda, Naho; Suganuma, Hiroki; Ohkawa, Natsuki; Nagata, Satoru; Shoji, Hiromichi; Shimizu, Toshiaki

    2014-08-01

    Enterococcus faecalis is rarely involved in neonatal meningitis. Several studies have indicated that the cytokines related to bacterial infection may induce nerve cell damage; therefore, the cytokine levels in cerebrospinal fluid (CSF) could represent a valuable hallmark for rapid recognition of the disease and evaluation of the degree of neurological involvement. We analyzed cytokine levels in the CSF of a neonate with E. faecalis meningitis over time. Tumor necrosis factor-? (TNF-?) tended to be elevated during the acute phase of infection, and then decreased during the convalescent stage after treatment. CSF inflammatory cytokine measurement may provide important clues for predicting the development of complications in the host because some of these cytokines, such as TNF-?, can injure neurons. PMID:25252071

  14. Detection of High Cerebrospinal Fluid Levels of (1?3)-?-d-Glucan in Cryptococcal Meningitis

    PubMed Central

    Rhein, Joshua; Bahr, Nathan C.; Morawski, Bozena M.; Schutz, Charlotte; Zhang, Yonglong; Finkelman, Malcolm; Meya, David B.; Meintjes, Graeme; Boulware, David R.

    2014-01-01

    Background ?(1?3)-?-d-Glucan (BDG) is a helpful diagnostic marker for many invasive fungal infections. However, BDG is not thought to be useful in diagnosing cryptococcosis. We evaluated the utility of BDG as an adjunct diagnostic tool for patients infected with human immunodeficiency virus (HIV) and presenting with suspected cryptococcal meningitis. Methods ?The Fungitell assay was used to measure BDG concentrations in cerebrospinal fluid (CSF) (n = 177) and serum (n = 109) of HIV-infected Ugandans and South Africans with suspected meningitis. Correlations between BDG concentrations and quantitative CSF cryptococcal cultures, CSF cryptococcal antigen (CRAG) titers, and 18 different CSF cytokine concentrations were assessed using non-parametric tests. Mixed models evaluated longitudinal changes in CSF BDG concentrations. Survival analyses were used to evaluate BDG's relationship with mortality. Results ?The Fungitell BDG assay provided 89% sensitivity and 85% specificity in CSF for cryptococcal meningitis. Serum sensitivity was suboptimal (79%). Cerebrospinal fluid BDG concentrations at diagnosis were median (interquartile range) 343 (200–597) pg/mL in cryptococcal patients and 37 (23–46) pg/mL in patients without cryptococcosis. Sensitivity in CSF improved to 98% (53 of 54) when initial fungal burdens were ?10 000 colony-forming units/mL. (1?3)-?-d-Glucan normalized rapidly after initiating antifungal therapy. Baseline BDG concentrations correlated with CSF fungal burden (rho = 0.820; P < .001), CSF CRAG lateral flow assay titers (rho = 0.780, P < .001), and monocyte chemotactic protein-1 levels in CSF (P = .047). In patients with cryptococcal meningitis, BDG ?500 pg/mL at diagnosis was associated with increased 10-week mortality. Conclusions ?(1?3)-?-d-Glucan is detectable in the CSF of HIV-infected patients with Cryptococcus, and it may provide useful prognostic information. Sensitivity is less than CRAG; however, BDG normalizes rapidly, unlike CRAG, making BDG potentially useful in diagnosing recurrent episodes. PMID:25734173

  15. Evaluation of hematological, serum biochemical and cerebrospinal fluid parameters in experimental bacterial meningitis in the calf.

    PubMed

    Nazifi, S; Rezakhani, A; Badran, M

    1997-03-01

    To evaluate the effects of bacterial meningitis on blood and CSF parameters, an experiment was conducted with five Iranian crossbred male calves. Blood and CSF samples were collected 3 times within a 5-day interval before the administration of bacteria for obtaining control values. Following the injection of E. coli, K12 into the cerebrospinal fluid from the lumbosacral space, samples were collected and clinical signs of meningitis were observed. Blood and CSF samples were obtained from the meningitis group 3 times at 1, 3, and 5 days post injection. The treatment of the infected calves using lincospectin and tetracycline was carried out immediately after the onset of clinical signs. After the treatment, blood and CSF samples were obtained 3 times during a 5-day period. Following the induction of meningitis, the number of WBCs, neutrophils, eosinophils and monocytes significantly increased (P < 0.05). However, the percent of lymphocytes decreased significantly (P < 0.05). The concentrations of glucose, potassium and activity of AST, LDH, CK significantly increased (P < 0.05). In contrast, the concentrations of phosphorous, sodium and magnesium significantly decreased (P < 0.05). Furthermore, following the induction of meningitis, the CSF was slightly xantochromic and turbid. The concentrations of protein, cholesterol, phosphorous, potassium, the activities of AST, LDH, CK, and the cell numbers in the CSF increased significantly (P < 0.05). In contrast, the concentration of glucose and pH in the CSF decreased significantly (P < 0.05). This study showed that bacterial meningitis can have profound effects on blood and CSF parameters which enable one to reach diagnosis. PMID:9123983

  16. Genetic Variation and Cerebrospinal Fluid Levels of Mannose Binding Lectin in Pneumococcal Meningitis Patients

    PubMed Central

    Brouwer, Matthijs C.; Baas, Frank; van der Ende, Arie; van de Beek, Diederik

    2013-01-01

    It has been suggested that genetic variants in mannose binding lectin (MBL2) influence susceptibility and outcome of invasive pneumococcal disease. We assessed the influence of genetic variation in MBL2 on susceptibility, outcome and causative serotype of pneumococcal meningitis in a prospective nationwide cohort study including 299 white patients and 216 controls. We assessed functionality of the genetic polymorphisms by measuring levels of MBL, C3a, iC3b, C5a and sC5b-9 in cerebrospinal fluid. We also performed a meta-analysis of studies on MBL2 polymorphisms and susceptibility to invasive pneumococcal disease. The risk of contracting pneumococcal meningitis was substantially increased for white individuals homozygous with the defective MBL2 0/0 genotype (odds ratio [OR] 8.21, 95% confidence interval [CI] 1.05–64.1; p?=?0.017). CSF MBL levels were significantly lower in patients with the A/0 and 0/0 genotype compared to homozygotes for the wild-type alleles (A/A; p<0.001). CSF MBL levels were positively correlated with C3a and iC3b levels, indicating complement activation by the lectin pathway. The effect of MBL2 genetic variants on susceptibility remained robust in a meta-analysis including 5 studies with 287 patients (OR 2.33, 99% CI 1.39–3.90). We conclude that MBL2 polymorphisms influence CSF MBL levels and substantially increase the risk of pneumococcal meningitis. PMID:23741476

  17. (1,3)-?-d-Glucan in Cerebrospinal Fluid for Diagnosis of Fungal Meningitis Associated with Contaminated Methylprednisolone Injections.

    PubMed

    Malani, Anurag N; Singal, Bonita; Wheat, L Joseph; Al Sous, Ola; Summons, Theresa A; Durkin, Michelle M; Pettit, April C

    2015-03-01

    Prompt diagnosis and treatment of fungal meningitis are critical, but culture is insensitive. (1,3)-?-d-Glucan (BDG) testing is FDA approved for serological diagnosis of invasive fungal disease; however, BDG testing is not approved for cerebrospinal fluid (CSF), and the appropriate cutoff value is unknown. We aimed to validate the diagnostic accuracy of CSF BDG measurements for fungal meningitis among patients exposed to contaminated methylprednisolone acetate (MPA). A retrospective observational study was conducted at St. Joseph Mercy Hospital and Vanderbilt University from November 2013 to February 2014. Patients were included if they had received a contaminated MPA injection. Cases were classified as probable or proven meningitis according to Centers for Disease Control and Prevention guidelines. CSF BDG testing was performed according to the package insert instructions for serum samples, and results were validated using Clinical and Laboratory Standards Institute procedures (MiraVista Diagnostics). Of 233 patients, 45 had meningitis (28 proven cases), 53 had spinal/paraspinal infections (19 proven cases), and 135 did not develop disease. Using the manufacturer's cutoff value (?80 pg/ml), the sensitivity and specificity were 96% and 95%, respectively, for proven meningitis and 84% and 95% for probable or proven meningitis. Receiver operating characteristic analysis identified the optimal cutoff value for proven meningitis to be 66 pg/ml (sensitivity, 100%; specificity, 94%) and that for probable or proven meningitis to be 66 pg/ml (sensitivity, 91%; specificity, 92%). Our results suggest that CSF BDG measurements are highly sensitive and specific for the diagnosis of fungal meningitis associated with contaminated MPA injections. Further study on the utility of CSF BDG testing for other types of fungal meningitis is needed. PMID:25540391

  18. Classification of frontal fossa fractures associated with cerebrospinal fluid rhinorrhea, pneumocephalus or meningitis. Indications and time for surgical treatment.

    PubMed

    Vrankovi?, D; Glavina, K

    1993-03-01

    The classification of anterior fossa fractures with their sequelae: cerebrospinal fluid (CSF) rhinorrhea, pneumocephalus, or meningitis is presented. This classification is based on five selection criteria which are discussed in this paper. This classification resulted in the table of indications for operative treatment, according to which the appropriate time for operation in urgent cases is immediately, in cases with absolute indication 5 to 6 days after the injury, in long-lasting CSF rhinorrhea or pneumocephalus 10 days after the onset, in intermittent or delayed rhinorrhea and/or pneumocephalus as soon as these signs occur, and in cases of meningitis soon after recovery. This study is based on the analysis of 52 consecutive surgically treated cases, collected from 1984 up to December 1989. PMID:8483509

  19. Demonstration of components of antigen 85 complex in cerebrospinal fluid of tuberculous meningitis patients.

    PubMed

    Kashyap, Rajpal S; Dobos, Karen M; Belisle, John T; Purohit, Hemant J; Chandak, Nitin H; Taori, Girdhar M; Daginawala, Hatim F

    2005-06-01

    Tuberculous meningitis (TBM) is the most common form of chronic infection of the central nervous system. Despite the magnitude of the problem, the general diagnostic outlook is discouraging. Specifically, there is no generally accepted early confirmative diagnosis protocol available for TBM. Various Mycobacterium tuberculosis antigens are now recognized as potential markers for diagnosis of TBM. However, their presence remains questionable, and many of these antigens are reported in the blood but not in the cerebrospinal fluid (CSF). This study identifies a specific protein marker in CSF which will be useful in early diagnosis of TBM. We have demonstrated the presence of a 30-kDa protein band in CSF of 100% (n = 5) of confirmed and 90% (n = 138) of suspected TBM patients out of 153 TBM patients. The 30-kDa band was excised from the gel, destained extensively, and digested with trypsin. The resulting peptides were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Partially purified proteins from CSF samples of TBM were analyzed by two-dimensional polyacrylamide gel electrophoresis and Western blotting. Immunoblotting and enzyme-linked immunosorbent assay (ELISA) were performed to confirm the presence of proteins in the 30-kDa protein band. The antigen 85 (Ag 85) complex was detected in CSF of TBM patients by indirect ELISA using antibodies against Ag 85 complex. The results of this study showed the 30-kDa protein band contained MTB proteins Rv3804c (Ag85A) and Rv1886c (Ag 85B), both members of the Ag85 complex. This was also confirmed by using immunotechniques such as indirect ELISA and the dot immunobinding assay. Detection of Ag85 complex was observed in CSF of 89% (71 out of 80) of suspected TBM patients that were 30-kDa protein positive. The observed 30-kDa protein in the CSF is comprised of the MTB Ag85 complex. This protein was earlier reported to be present in the blood of patients with extra-central nervous system tuberculosis. Therefore, this finding suggests that this protein can be used as a molecular marker for any type of tuberculous infection. It also provides a more sensitive immunoassay option for the early and confirmatory diagnosis of TBM. PMID:15939750

  20. Meningeal Inflammation Increases Artemether Concentrations in Cerebrospinal Fluid in Papua New Guinean Children Treated with Intramuscular Artemether ?

    PubMed Central

    Manning, Laurens; Laman, Moses; Page-Sharp, Madhu; Salman, Sam; Hwaiwhanje, Ilomo; Morep, Namar; Siba, Peter; Mueller, Ivo; Karunajeewa, Harin A.; Davis, Timothy M. E.

    2011-01-01

    Although the artemisinin-associated neurotoxicity identified in vitro and in animal studies has not been confirmed clinically, only one adult study has measured cerebrospinal fluid (CSF) concentrations after administration of conventional doses. Potential artemisinin neurotoxicity could be serious in children, especially those with meningitis and, consequently, a compromised blood-brain barrier. We measured CSF/plasma artemether and dihydroartemisinin (DHA) concentrations in 32 Papua New Guinean children with a mean age of 39 months with suspected or proven severe falciparum malaria who underwent a single lumbar puncture after intramuscular artemether administration. CSF artemether concentrations were 0 to 43.5 ?g/liter and CSF concentration/plasma concentration ratios were 0 to 38.1%. DHA was measurable in CSF in only two children. The seven children with meningeal inflammation (CSF white cell count > 20/mm3) had higher CSF artemether concentration/plasma artemether concentration ratios than those without (median, 6.7% [interquartile ratio, 2.5 to 27.8%]% versus 0.0% [interquartile ratio, 0.0 to 2.5%]; P = 0.002). Meningeal inflammation was associated with a 4.6-fold increase in the CSF artemether concentration/plasma artemether concentration ratio in a population pharmacokinetic model. These data suggest that pharmacovigilance should be heightened when intramuscular artemether is given to severely ill children with evidence of meningeal inflammation. PMID:21859936

  1. Cerebrospinal fluid lactate concentration to distinguish bacterial from aseptic meningitis: a systemic review and meta-analysis

    PubMed Central

    2010-01-01

    Introduction Making a differential diagnosis between bacterial meningitis and aseptic meningitis is a critical clinical problem. The utility of a cerebrospinal fluid (CSF) lactate assay for this purpose has been debated and is not yet routinely clinically performed. To adequately evaluate this assay, a systematic review and meta-analysis of studies of the CSF lactate concentration as a marker for both bacterial meningitis and aseptic meningitis was performed. Methods Electronic searches in PubMed, Scopus, the MEDION database and the Cochrane Library were conducted to identify relevant articles published before March 2009. A manual search of reference lists from selected articles was also conducted. Two reviewers independently selected relevant articles and extracted data on study characteristics, quality and accuracy. Results Twenty-five articles were identified that met the eligibility criteria. Diagnostic odds ratios were considerably homogenous (Chi-square P = 0.1009, I2 = 27.6%), and the homogeneity was further confirmed by a Galbraith plot and meta-regression analysis using several covariates. The symmetrical summary receiver-operator characteristic curve (SROC), fitted using the Moses-Shapiro-Littenberg method, was positioned near the upper left corner of the SROC curve. The Q value and area under the curve were 0.9451 and 0.9840, respectively, indicating excellent accuracy. The diagnostic accuracy of the CSF lactate concentration was higher than those of other four conventional markers (CSF glucose, CSF/plasma glucose quotient, CSF protein, and CSF total number of leukocytes) using a head to head meta-analysis of the 25 included studies. Conclusions To distinguish bacterial meningitis from aseptic meningitis, CSF lactate is a good single indicator and a better marker compared to other conventional markers. PMID:21194480

  2. Antimicrobial sensitivity patterns of cerebrospinal fluid (CSF) isolates in Namibia: implications for empirical antibiotic treatment of meningitis

    PubMed Central

    2013-01-01

    Objective Bacterial meningitis is a medical emergency associated with high mortality rates. Cerebrospinal fluid (CSF) culture is the “gold standard” for diagnosis of meningitis and it is important to establish the susceptibility of the causative microorganism to rationalize treatment. The Namibia Standard Treatment Guidelines (STGs) recommends initiation of empirical antibiotic treatment in patients with signs and symptoms of meningitis after taking a CSF sample for culture and sensitivity. The objective of this study was to assess the antimicrobial sensitivity patterns of microorganisms isolated from CSF to antibiotics commonly used in the empirical treatment of suspected bacterial meningitis in Namibia. Methods This was a cross-sectional descriptive study of routinely collected antibiotic susceptibility data from the Namibia Institute of Pathology (NIP) database. Results of CSF culture and sensitivity from January 1, 2009 to May 31, 2012, from 33 state hospitals throughout Namibia were analysed. Results The most common pathogens isolated were Streptococcus species, Neisseria meningitidis, Haemophilus influenzae, Staphylococcus, and Escherichia coli. The common isolates from CSF showed high resistance (34.3% –73.5%) to penicillin. Over one third (34.3%) of Streptococcus were resistance to penicillin which was higher than 24.8% resistance in the United States. Meningococci were susceptible to several antimicrobial agents including penicillin. The sensitivity to cephalosporins remained high for Streptococcus, Neisseria, E. coli and Haemophilus. The highest percentage of resistance to cephalosporins was seen among ESBL K. pneumoniae (n?=?7, 71%–100%), other Klebsiella species (n?=?7, 28%–80%), and Staphylococcus (n?=?36, 25%–40%). Conclusions The common organisms isolated from CSF were Streptococcus Pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Staphylococcus, and E. coli. All common organisms isolated from CSF showed high sensitivity to cephalosporins used in the empirical treatment of meningitis. The resistance of the common isolates to penicillin is high. Most ESBL K. pneumoniae were isolated from CSF samples drawn from neonates and were found to be resistant to the antibiotics recommended in the Namibia STGs. Based on the above findings, it is recommended to use a combination of aminoglycoside and third-generation cephalosporin to treat non–ESBL Klebsiella isolates. Carbapenems (e.g., meropenem) and piperacillin/tazobactam should be considered for treating severely ill patients with suspected ESBL Klebsiella infection. Namibia should have a national antimicrobial resistance surveillance system for early detection of antibiotics that may no longer be effective in treating meningitis and other life-threatening infections due to resistance. PMID:24764539

  3. Cerebrospinal fluid immunoglobulins in children.

    PubMed Central

    Gill, D G; Brody, M

    1979-01-01

    Cerebrospinal fluid (CSF) immunoglobulins were measured in 62 normal children, in 9 children with purulent meningitis, and in 10 children with presumptive viral meningitis. The mean values in normal children were IgA 0, IgM 0, and IgG 0.84 +/- 1.4 mg/100 ml (+/- SD). The mean levels of all CSF immunoglobulins were raised in acute bacterial meningitis and were significantly greater than the levels found in viral meningitis. CSF IgM was 0.16 +/- 0.5 mg/100 ml in viral meningitis compared with 2.64 +/- 2.06 mg/100 ml in bacterial meningitis (P less than 0.01). However, these values overlapped to a considerable extent and, generally, measurement of CSF immunoglobulins did not enhance diagnostic accuracy in this group of children. PMID:533301

  4. Tumor necrosis factor alpha in cerebrospinal fluid during bacterial, but not viral, meningitis. Evaluation in murine model infections and in patients

    PubMed Central

    1988-01-01

    To evaluate the potential role of cachectin/TNF-alpha in the pathogenesis of bacterial and viral meningitis, concentrations and kinetics of TNF-alpha were determined in cerebrospinal fluid (CSF). After intracerebral, but not systemic, infection with Listeria monocytogenes in mice, TNF-alpha was detected as early as 3 h after infection reaching maximum titers after 24 h. However, TNF-alpha was not found in serum during the course of Listeria infection. In contrast to bacterial meningitis, no TNF-alpha was detected at any time in CSF of mice suffering from severe lymphocytic choriomeningitis induced by intracerebral infection with lymphocytic choriomeningitis virus. This difference is striking since both model infections led to a massive infiltration of polymorphonuclear and mononuclear leukocytes into the meninges and CSF. The results found for the two model infections were paralleled by findings in humans; CSF from three out of three patients with bacterial meningitis examined during the first day of hospitalization showed significant levels of TNF-alpha; none of the CSF obtained later than 3 d after hospitalization was positive. In addition, similarly to what was found in mice with viral meningitis, zero out of seven patients with viral meningitis had detectable TNF- alpha in CSF. PMID:3367098

  5. Cerebrospinal Fluid Cytokine Profiles Predict Risk of Early Mortality and Immune Reconstitution Inflammatory Syndrome in HIV-Associated Cryptococcal Meningitis.

    PubMed

    Jarvis, Joseph N; Meintjes, Graeme; Bicanic, Tihana; Buffa, Viviana; Hogan, Louise; Mo, Stephanie; Tomlinson, Gillian; Kropf, Pascale; Noursadeghi, Mahdad; Harrison, Thomas S

    2015-04-01

    Understanding the host immune response during cryptococcal meningitis (CM) is of critical importance for the development of immunomodulatory therapies. We profiled the cerebrospinal fluid (CSF) immune-response in ninety patients with HIV-associated CM, and examined associations between immune phenotype and clinical outcome. CSF cytokine, chemokine, and macrophage activation marker concentrations were assayed at disease presentation, and associations between these parameters and microbiological and clinical outcomes were examined using principal component analysis (PCA). PCA demonstrated a co-correlated CSF cytokine and chemokine response consisting primarily of Th1, Th2, and Th17-type cytokines. The presence of this CSF cytokine response was associated with evidence of increased macrophage activation, more rapid clearance of Cryptococci from CSF, and survival at 2 weeks. The key components of this protective immune-response were interleukin (IL)-6 and interferon-?, IL-4, IL-10 and IL-17 levels also made a modest positive contribution to the PC1 score. A second component of co-correlated chemokines was identified by PCA, consisting primarily of monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1? (MIP-1?). High CSF chemokine concentrations were associated with low peripheral CD4 cell counts and CSF lymphocyte counts and were predictive of immune reconstitution inflammatory syndrome (IRIS). In conclusion CSF cytokine and chemokine profiles predict risk of early mortality and IRIS in HIV-associated CM. We speculate that the presence of even minimal Cryptococcus-specific Th1-type CD4+ T-cell responses lead to increased recruitment of circulating lymphocytes and monocytes into the central nervous system (CNS), more effective activation of CNS macrophages and microglial cells, and faster organism clearance; while high CNS chemokine levels may predispose to over recruitment or inappropriate recruitment of immune cells to the CNS and IRIS following peripheral immune reconstitution with ART. These results provide a rational basis for future studies of immune modulation in CM, and demonstrate the potential of baseline immune profiling to identify CM patients most at risk of mortality and subsequent IRIS. PMID:25853653

  6. Cerebrospinal Fluid Cytokine Profiles Predict Risk of Early Mortality and Immune Reconstitution Inflammatory Syndrome in HIV-Associated Cryptococcal Meningitis

    PubMed Central

    Jarvis, Joseph N.; Meintjes, Graeme; Bicanic, Tihana; Buffa, Viviana; Hogan, Louise; Mo, Stephanie; Tomlinson, Gillian; Kropf, Pascale; Noursadeghi, Mahdad; Harrison, Thomas S.

    2015-01-01

    Understanding the host immune response during cryptococcal meningitis (CM) is of critical importance for the development of immunomodulatory therapies. We profiled the cerebrospinal fluid (CSF) immune-response in ninety patients with HIV-associated CM, and examined associations between immune phenotype and clinical outcome. CSF cytokine, chemokine, and macrophage activation marker concentrations were assayed at disease presentation, and associations between these parameters and microbiological and clinical outcomes were examined using principal component analysis (PCA). PCA demonstrated a co-correlated CSF cytokine and chemokine response consisting primarily of Th1, Th2, and Th17-type cytokines. The presence of this CSF cytokine response was associated with evidence of increased macrophage activation, more rapid clearance of Cryptococci from CSF, and survival at 2 weeks. The key components of this protective immune-response were interleukin (IL)-6 and interferon-?, IL-4, IL-10 and IL-17 levels also made a modest positive contribution to the PC1 score. A second component of co-correlated chemokines was identified by PCA, consisting primarily of monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1? (MIP-1?). High CSF chemokine concentrations were associated with low peripheral CD4 cell counts and CSF lymphocyte counts and were predictive of immune reconstitution inflammatory syndrome (IRIS). In conclusion CSF cytokine and chemokine profiles predict risk of early mortality and IRIS in HIV-associated CM. We speculate that the presence of even minimal Cryptococcus-specific Th1-type CD4+ T-cell responses lead to increased recruitment of circulating lymphocytes and monocytes into the central nervous system (CNS), more effective activation of CNS macrophages and microglial cells, and faster organism clearance; while high CNS chemokine levels may predispose to over recruitment or inappropriate recruitment of immune cells to the CNS and IRIS following peripheral immune reconstitution with ART. These results provide a rational basis for future studies of immune modulation in CM, and demonstrate the potential of baseline immune profiling to identify CM patients most at risk of mortality and subsequent IRIS. PMID:25853653

  7. Diagnostic Accuracy of Presepsin (sCD14-ST) for Prediction of Bacterial Infection in Cerebrospinal Fluid Samples from Children with Suspected Bacterial Meningitis or Ventriculitis.

    PubMed

    Stubljar, David; Kopitar, Andreja Natasa; Groselj-Grenc, Mojca; Suhadolc, Kristina; Fabjan, Teja; Skvarc, Miha

    2015-04-01

    Children with temporary external ventricular drains (EVD) are prone to nosocomial infections. Diagnosis of bacterial meningitis and ventriculitis in these children is challenging due to frequent blood contamination of cerebrospinal fluid (CSF) and the presence of chemical ventriculitis. The aim of this study was to compare diagnostic accuracy of presepsin (sCD14-ST), a novel biomarker of bacterial infection in CSF, to predict bacterial infection in comparison to the accuracy of established biomarkers like those demonstrated in biochemical analysis of CSF. We conducted a prospective study with 18 children with suspected bacterial meningitis or ventriculitis who had 66 episodes of disease. CSF samples were taken from external ventricular drainage. We measured presepsin in CSF, as well as CSF leukocyte count, glucose, and proteins. CSF was also taken to prove bacterial infection with culture methods or with 16S rRNA gene broad-range PCR (SepsiTest; Molzym, Germany). Infection was clinically confirmed in 57 (86%) episodes of suspected meningitis or ventriculitis. Chemical ventriculitis was diagnosed in 9 (14%) episodes of suspected meningitis or ventriculitis. Diagnostic accuracies presented as area under the curve (AUC) for sCD14-ST, leukocytes, and proteins measured in CSF were 0.877 (95% confidence interval [CI], 0.793 to 0.961), 0.798 (95% CI, 0.677 to 0.920), and 0.857 (95% CI, 0.749 to 0.964), respectively. With CSF culture, we detected bacteria in 17 samples, compared to 37 detected with broad-range PCR. It was found that presepsin was present at a significantly higher level in children with clinically proven ventriculitis than in those without meningitis or ventriculitis. Diagnostic accuracies of presepsin were superior to those of leukocytes or proteins in CSF. Presepsin-guided 16S rRNA gene PCR could be used in everyday clinical practice to improve etiological diagnosis of meningitis and ventriculitis and to prescribe more appropriate antibiotics. PMID:25653398

  8. Climate Change and Cerebrospinal Meningitis in the Ghanaian Meningitis Belt

    PubMed Central

    Codjoe, Samuel Nii Ardey; Nabie, Vivian Adams

    2014-01-01

    Cerebrospinal meningitis (CSM) is one of the infectious diseases likely to be affected by climate change. Although there are a few studies on the climate change-CSM nexus, none has considered perceptions of community members. However, understanding public perception in relation to a phenomenon is very significant for the design of effective communication and mitigation strategies as well as coping and adaptation strategies. This paper uses focus group discussions (FGDs) to fill this knowledge lacuna. Results show that although a few elderly participants ascribed fatal causes (disobedience to gods, ancestors, and evil spirits) to CSM infections during FGDs, majority of participants rightly linked CSM infections to dry, very hot and dusty conditions experienced during the dry season. Finally, community members use a suite of adaptation options to curb future CSM epidemics. PMID:25003550

  9. Meningeal derived cerebrospinal fluid proteins in different forms of dementia: is a meningopathy involved in normal pressure hydrocephalus?

    PubMed Central

    Brettschneider, J; Riepe, M; Petereit, H; Ludolph, A; Tumani, H

    2004-01-01

    Methods: We analysed the cerebrospinal fluid (CSF) concentrations of the leptomeningeal derived ß trace protein, ß2 microglobulin, and cystatin C. Results: There was a statistically significant difference of the CSF ß trace protein levels among different groups. Patients with idiopathic normal pressure hydrocephalus (NPH) (17.5 (SD 4.3) mg/l) showed significantly lower CSF ß trace protein levels than patients with Alzheimer's disease (23.8 (6.2) mg/l), depression (24.2 (7.3) mg/l), and normal controls (25.3 (4.9) mg/l). To patients with vascular dementia (20.1 (5.6) mg/l) and frontotemporal dementia (21.9 (7.0) mg/l), the difference was not significant. There was no significant difference regarding the CSF and serum concentrations of ß2 microglobulin or cystatin C among the different groups. Conclusions: We conclude that leptomeningeal dysfunction may be involved in certain types of dementia such as NPH and that reduced CSF ß trace protein levels in patients with NPH may aid in differentiating this difficult to diagnose disorder from other syndromes such as Alzheimer's disease. PMID:15489398

  10. RESEARCH ARTICLE Open Access Lipocalin 2 in cerebrospinal fluid as a marker of

    E-print Network

    Boyer, Edmond

    , Inflammation, Cerebrospinal fluid, Diagnosis Background Acute bacterial meningitis (ABM) is a major cause is a medical emergency and requires immediate management that relies mainly on appropriate and prompt

  11. Initial Antituberculous Regimen with Better Drug Penetration into Cerebrospinal Fluid Reduces Mortality in HIV Infected Patients with Tuberculous Meningitis: Data from an HIV Observational Cohort Study

    PubMed Central

    Midde, Manoranjan; Pakam, Raghavakalyan; Naik, Praveen Kumar

    2013-01-01

    Tuberculous meningitis (TM) is the deadliest form of tuberculosis. Nearly two-thirds of HIV infected patients with TM die, and most deaths occur within one month. Current treatment of TM involves the use of drugs with poor penetration into the cerebro-spinal fluid (CSF). In this study, we present the mortality before and after implementing a new antituberculous regimen (ATR) with a higher drug penetration in CSF than the standard ATR during the initial treatment of TM in an HIV cohort study. The new ATR included levofloxacin, ethionamide, pyrazinamide, and a double dose of rifampicin and isoniazid and was given for a median of 7 days (interquartile range 6–9). The new ATR was associated with an absolute 21.5% (95% confidence interval (CI), 7.3–35.7) reduction in mortality at 12 months. In multivariable analysis, independent factors associated with mortality were the use of the standard ATR versus the new ATR (hazard ratio 2.05; 95% CI, 1.2–3.5), not being on antiretroviral therapy, low CD4 lymphocyte counts, and low serum albumin levels. Our findings suggest that an intensified initial ATR, which likely results in higher concentrations of active drugs in CSF, has a beneficial effect on the survival of HIV-related TM. PMID:23997952

  12. iTRAQ-based quantitative proteomic analysis of cerebrospinal fluid reveals NELL2 as a potential diagnostic biomarker of tuberculous meningitis.

    PubMed

    Yang, Yongtao; Mu, Jun; Chen, Guanghui; Zhan, Yuan; Zhong, Jiaju; Wei, Youdong; Cheng, Ke; Qin, Bin; You, Hongmin; Xie, Peng

    2015-05-01

    Tuberculous meningitis (TBM) is a serious complication of tuberculosis that affects the central nervous system. As TBM may result in permanent sequelae and death, rapid, accurate diagnostic tests using novel biomarkers are required for the early diagnosis and treatment of TBM. A quantitative proteomic study was therefore performed to identify differential proteins in the cerebrospinal fluid (CSF) obtained from TBM patients (n=12) and healthy controls (n=12). CSF samples were labelled with iTRAQ™ and analyzed by LC?MS/MS. Gene ontology and Pathway analysis were conducted using DAVID bioinformatics resources. Neural epidermal growth factor?like like 2 (NELL2) with the largest fold?change value was selected for validation by western blotting. Proteomic phenotyping revealed over?representation in two inflammation?associated processes, complement and coagulation cascades as well as cell adhesion molecules. Western blotting showed a significant decrease in NELL2 levels in TBM subjects compared to healthy controls. The AUC analysis revealed NELL2 was able to distinguish TBM subjects from healthy controls with 83.3% sensitivity and 75% specificity. In conclusion, the results showed that CSF NELL2 is a potential diagnostic biomarker for TBM. Further evaluation of these findings in larger studies including anti?tuberculosis medicated and unmedicated patient cohorts with other intracranial infectious diseases is required for clinical translation. PMID:25760060

  13. Survival Defects of Cryptococcus neoformans Mutants Exposed to Human Cerebrospinal Fluid Result in Attenuated Virulence in an Experimental Model of Meningitis? †

    PubMed Central

    Lee, Anthony; Toffaletti, Dena L.; Tenor, Jennifer; Soderblom, Erik J.; Thompson, J. Will; Moseley, M. Arthur; Price, Michael; Perfect, John R.

    2010-01-01

    Cryptococcus neoformans is a fungal pathogen that encounters various microenvironments during growth in the mammalian host, including intracellular vacuoles, blood, and cerebrospinal fluid (CSF). Because the CSF is isolated by the blood-brain barrier, we hypothesize that CSF presents unique stresses that C. neoformans must overcome to establish an infection. We assayed 1,201 mutants for survival defects in growth media, saline, and human CSF. We assessed CSF-specific mutants for (i) mutant survival in both human bronchoalveolar lavage (BAL) fluid and fetal bovine serum (FBS), (ii) survival in macrophages, and (iii) virulence using both Caenorhabditis elegans and rabbit models of cryptococcosis. Thirteen mutants exhibited significant survival defects unique to CSF. The mutations of three of these mutants were recreated in the clinical serotype A strain H99: deletions of the genes for a cation ATPase transporter (ena1?), a putative NEDD8 ubiquitin-like protein (rub1?), and a phosphatidylinositol 4-kinase (pik1?). Mutant survival rates in yeast media, saline, and BAL fluid were similar to those of the wild type; however, survival in FBS was reduced but not to the levels in CSF. These mutant strains also exhibited decreased intracellular survival in macrophages, various degrees of virulence in nematodes, and severe attenuation of survival in a rabbit meningitis model. We analyzed the CSF by mass spectrometry for candidate compounds responsible for the survival defect. Our findings indicate that the genes required for C. neoformans survival in CSF ex vivo are necessary for survival and infection in this unique host environment. PMID:20696827

  14. Cerebrospinal fluid zinc concentrations in febrile convulsions.

    PubMed Central

    Garty, B Z; Olomucki, R; Lerman-Sagie, T; Nitzan, M

    1995-01-01

    Zinc modulates the activity of glutamic acid decarboxylase, the rate limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter. Low cerebrospinal fluid GABA values have been reported in association with several seizure disorders, including febrile convulsions. It is also known that fever and/or infections may cause a reduction in serum zinc concentrations. In this study the hypothesis that febrile convulsions are related to low cerebrospinal fluid zinc was tested. Cerebrospinal fluid zinc concentrations were measured in 66 febrile children: 32 with febrile convulsions, 18 with fever but without convulsions, and 16 with aseptic (viral) meningitis. There was no statistically significant difference in the cerebrospinal fluid zinc between the three groups of children, and the mean concentration was 26.2 micrograms/l. No significant relationship was found between either age, gender, maximal temperature, type of infection, or time of performance of the lumbar puncture and cerebrospinal fluid zinc concentration. These results do not support the hypothesis that febrile convulsions are related to reduced cerebrospinal fluid zinc concentrations. PMID:7492199

  15. Low cerebrospinal fluid pressure headache

    Microsoft Academic Search

    Christine M. Lay

    2002-01-01

    Opinion statement  \\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a Alterations in cerebrospinal fluid (CSF) pressure lead to neurologic symptoms, the most common clinical manifestation of which\\u000a is headache. Typically, the headache is orthostatic and related to traction on pain-sensitive intracranial and meningeal structures,\\u000a distention on periventricular pain-sensitive areas, and direct pressure on pain conveying cranial nerves.\\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a Low CSF headache is a distinct and familiar syndrome

  16. Cerebrospinal fluid culture

    MedlinePLUS

    If bacteria are present, you may have bacterial meningitis . Other possible infections include tuberculosis and fungal infections. ... the infection is contagious, unless it is meningococcal meningitis. See also: Aseptic meningitis Cryptococcosis

  17. Cerebrospinal Fluid Leaks of Temporal Bone Origin: Etiology and Management

    Microsoft Academic Search

    Mark Stenzel; Simon Preuss; Lisa Orloff; Peter Jecker; Wolf Mann

    2005-01-01

    Background: Cerebrospinal fluid (CSF) leaks of the temporal bone region require surgical treatment as they pose life-threatening risks such as meningitis. Aim: The aim of the study was to determine the surgical outcome depending on different operation techniques and grafts. Method: We performed a retrospective review of 28 cases of CSF leaks, operated in our department from 1983 to 2002.

  18. Genome Sequence of Mycobacterium tuberculosis C2, a Cerebrospinal Fluid Clinical Isolate from Central India

    PubMed Central

    Bhullar, Shradha S.; More, Ravi P.; Puranik, Sampada; Taori, Girdhar M.; Daginawala, Hatim F.

    2014-01-01

    We report the annotated genome sequence of a Mycobacterium tuberculosis clinical isolate from the cerebrospinal fluid of a tuberculous meningitis patient admitted to the Central India Institute of Medical Sciences, Nagpur, India. PMID:25146143

  19. Evaluation of co-agglutination (COA), counter immunoelectrophoresis (CIE), culture and direct microscopic (Dm) examination of cere-brospinal fluid (CSF) for detection of meningitis caused by common bacterial pathogens.

    PubMed

    Chowdhury, Z U; Rahman, K M; Miah, R A; Hussain, T; Asna, Z H; Khan, W A

    1990-06-01

    Cerebrospinal fluid from 260 children clinically diagnosed as meningitis were examined by Dm, culture, COA and CIE test. Dm revealed the presence of bacteria in 41 (15.8%) whereas culture showed growth of organism in 52 (20%) cases. COA and CIE test were done for the detection of antigen of H. influenzae, S. pneumoniae and N. meningitidis. Among the 3 methods viz. culture, COA and CIE test which were used for the detection of the above three organisms COA detected the maximum numbers (23.5%). COA test could detect antigen in both culture positive and culture negative CSF samples. COA test detected 100% of pneumococcal, 88.5% of H. influenzae and 66.7% of N. meningitidis antigens from CSF. Diagnosis by CIE in detecting H. influenzae and N. meningitidis antigens is inferior to culture and COA, whereas in detecting pneumococcal antigens CIE is superior to culture. So COA is a valuable, cheap, rapid and sensitive method for the diagnosis of meningitis caused by the above three organisms and when used along with culture 100% of cases can be diagnosed. PMID:2205198

  20. Broad-Range 16S rRNA PCR with Cerebrospinal Fluid May Be Unreliable for Management of Postoperative Aseptic Meningitis ?

    PubMed Central

    Zarrouk, Virginie; Leflon-Guibout, Véronique; Robineaux, Sébastien; Kalamarides, Michel; Nicolas-Chanoine, Marie-Hélène; Sterkers, Olivier; Fantin, Bruno

    2010-01-01

    We previously demonstrated that discontinuing presumptive antibiotic treatment in cases of negative conventional cultures is safe and effective for patients with postoperative aseptic meningitis (PAM). Here, we prospectively investigated 32 patients with postoperative meningitis. All 26 patients with PAM diagnosed on the basis of conventional cultures demonstrated negative 16S rRNA PCR results. Our results suggest that the PCR technique does not change PAM management. PMID:20592153

  1. Confocal Raman microscopy of pathologic cells in cerebrospinal fluid

    NASA Astrophysics Data System (ADS)

    Gonchukov, S. A.; Lonkina, T. V.; Minaeva, S. A.; Sundukov, A. V.; Migmanov, T. E.; Lademann, J.; Darvin, M. E.; Bagratashvili, V. N.

    2014-01-01

    In this work, the spatial localization of leucocytes, bacteria, and erythrocytes in the crystal pattern of a dried droplet of cerebrospinal fluid (CSF) is established. Characteristic lines are detected and identified in the Raman spectrum of the CSF that point to the presence of pathologic cells therein and can be used in a timely way to diagnose meningitis, the spectroscopic sample preparation procedure being simple enough. A dry CSF sample retains its characteristic spectral features for no less than three days, which is important for its safe keeping and transportation, and also for the computer processing of its spectra.

  2. [Massive pneumocephalus and cerebrospinal fluid fistula after thoracotomy].

    PubMed

    Olarra, J; Longarela, A

    2008-10-01

    We report the case of a 70-year-old man (ASA physical status 2) who developed massive pneumocephalus caused by a fistula between the subarachnoid and pleural spaces following a left pneumonectomy. After an uneventful immediate postoperative period, the patient was readmitted to the recovery care unit with dyspnea, intense headache, confusion, and diminished level of consciousness. Computed tomography confirmed a cerebrospinal fluid fistula secondary to the opening of the intradural space during tumor resection. Treatment was conservative, consisting of rest in a slightly Trendelenburg position, antibiotic prophylaxis to prevent meningitis, and a water seal on the thoracic drainage tube. PMID:18982788

  3. Temporary reversal of serum to cerebrospinal fluid glycerol concentration gradient after intravenous infusion of glycerol

    Microsoft Academic Search

    R. Nau; F.-J. Prins; H. Kolenda; H. W. Prange

    1992-01-01

    Glycerol 50 g infused i. v. over 2 to 6 h is widely used to treat cerebral oedema in patients with acute stroke. Its transit through the blood-cerebrospinal fluid barrier in subjects with uninflamed meninges has now been examined. In 7 patients with an external ventriculostomy for occlusive hydrocephalus, each of whom was given 500 ml of a 10% solution

  4. [A case of cerebrospinal fluid hypovolemia caused by Ommaya reservoir successfully treated by epidural blood patch].

    PubMed

    Jimbo, Yasushi; Uzuka, Takeo; Fujii, Yukihiko

    2008-07-01

    Here, we report a case of cerebrospinal fluid hypovolemia caused by lumbar puncture for implantation of an Ommaya reservoir. A 55-year-old man with central nervous system lymphoma developed meningeal dissemination. He was treated by spinal radiotherapy, and had an Ommaya reservoir implanted for intrathecal injection of anticancer drugs. After one month, he complained of orthostatic neck pain. MRI revealed bilateral subdural effusion and diffuse meningeal enhancement. He was diagnosed as having cerebrospinal fluid hypovolemia. Because no improvement in symptoms was seen after 2 weeks of conservative treatment, he was treated by a lumbar epidural blood patch. Subsequently symptoms improved markedly, and bilateral subdural effusion and diffuse meningeal enhancement disappeared on follow-up MRI. PMID:18634407

  5. Cerebrospinal fluid leak presenting as oculorrhea after blunt orbitocranial trauma.

    PubMed

    Apkarian, Alexandra O; Hervey-Jumper, Shawn L; Trobe, Jonathan D

    2014-09-01

    Cerebrospinal fluid (CSF) leak is an uncommon but well-documented occurrence after blunt head trauma, typically manifesting as otorrhea or rhinorrhea. Blunt cranio-orbital trauma also may cause CSF leak into the orbit, manifesting as orbitocele, blepharocele, chemosis, or tearing ("oculorrhea"). We report a patient who developed oculorrhea after blunt head trauma, and neuroimaging disclosed comminuted fractures of the left frontal, greater sphenoid wing, nasal, and maxillary bones. Because he also displayed chemosis and markedly reduced ocular ductions and periocular pain, carotid-cavernous fistula was suspected but appropriate vascular imaging was negative. Aspiration of subconjunctival fluid was positive for beta-2 transferrin, a specific marker for CSF. Chemosis lessened and the oculorrhea ceased spontaneously within 6 days of the trauma. This manifestation of CSF leak must not be overlooked because of the threat of meningitis. PMID:24621864

  6. Cerebrospinal fluid shunt infection by Neisseria sicca.

    PubMed

    Hornyik, G; Piatt, J H

    1994-01-01

    Neisseria sicca is considered to be a nonpathogenic oral saprophyte. Presented here is an unusual case of cerebrospinal fluid (CSF) shunt infection by N. sicca. Although medical management of the common community-acquired meningitides, including infection by Neisseria meningitidis, is often successful in patients with CSF shunts, removal and replacement of the infected shunt was necessary in this case. PMID:7803309

  7. Cerebrospinal Fluid Shunt Infection by Neisseria sicca

    Microsoft Academic Search

    Galina Hornyik

    1994-01-01

    Neisseria sicca is considered to be a nonpathogenic oral saprophyte. Presented here is an unusual case of cerebrospinal fluid (CSF) shunt infection by N. sicca. Although medical management of the common community-acquired meningitides, including infection by Neisseria meningitidis, is often successful in patients with CSF shunts, removal and replacement of the infected shunt was necessary in this case.

  8. Cerebrospinal fluid shunt infections in children

    Microsoft Academic Search

    Mario Ammirati; Anthony J. Raimondi

    1987-01-01

    A total of 431 patients who underwent their first cerebrospinal fluid shunt insertion at Children's Memorial Hospital over a 10-year period were retrospectively studied with regard to the relationship between the etiology of the hydrocephalus, age at the time of shunt placement, and infection rate. Forty percent of the patients had constrictive hydrocephalus and meningomyelocele, 33% congenital communicating or obstructive

  9. Paradoxical Postural Headaches in Cerebrospinal Fluid Leaks

    Microsoft Academic Search

    B Mokri; A J Aksamit; J LD Atkinson

    2004-01-01

    Two patients with cerebrospinal fluid (CSF) leak, one at the level of fourth thoracic spine and another with undetermined level of leak, presented with paradoxical postural headaches in that the headaches were present when in a horizontal position and resolved if the patients were upright. One patient improved spontaneously and the other responded to a targeted epidural blood patch. Paradoxical

  10. Arginine vasopressin concentrations in the cerebrospinal fluid of children.

    PubMed

    Cotton, M F; Donald, P R; Aalbers, C

    1991-11-01

    Cerebrospinal fluid (CSF) arginine vasopressin (AVP) levels are reported in a group of 22 children (median age 24 months) investigated for possible bacterial meningitis and subsequently found not to be suffering from this disease. The mean CSF AVP concentration was 0.80 +/- 0.33 pg/ml. The results obtained in patients suffering from febrile convulsions (mean 0.71 pg/ml), other convulsive disorders (mean 0.80 pg/ml) and miscellaneous infectious diseases (mean 0.85 pg/ml) did not differ significantly from one another. Our findings confirm the presence of AVP in the CSF of children and provide reference values for further investigations into the functions of CSF AVP in children. PMID:1794121

  11. Two consecutive cases of cerebrospinal fluid rhinorrhea after septoplasty operation.

    PubMed

    Onerci, T Metin; Ayhan, Keramettin; O?retmeno?lu, O?uz

    2004-01-01

    Our aim in this work is to define the importance of anatomical knowledge in septoplasty operation and to prevent complications. Septoplasty is one of the most common operations in otorhinolaryngology to treat the nasal obstruction caused by septal deviation. During and after septoplasty, there are some recorded complications, such as hemorrhage, hematoma, septal abscess, septal perforation, saddle nose, infection, anosmia, visual disturbances, cavernous sinus thrombosis, meningitis, pneumoencephalos, subarachnoid hemorrhage, subdural empyma, brain abscess, periorbital emphysema, toxic shock syndrome, and cerebrospinal fluid (CSF) rhinorrhea. Some of the complications are rare, but their results are life threatening. We report a rare complication of septoplasty CSF rhinorrhea. Two consecutive cases of CSF fistulas after septoplasty operation are presented. Both of the cases were treated endoscopically. The possible mechanisms and different treatment options are discussed. Prevention of the CSF fistula in septoplasty is more important than its treatment. Realizing the anatomic variations and gentle manipulation at the ethmoid roof is essential. PMID:15334401

  12. Spectrophotometry for cerebrospinal fluid pigment analysis

    Microsoft Academic Search

    Axel Petzold; Lindsay T. Sharpe; Geoffrey Keir

    2006-01-01

    The use of spectrophotometry for the analysis of the cerebrospinal fluid (CSF) is reviewed The clinically relevant CSF pigments—oxyhemoglobin\\u000a and bilirubin—are introduced and discussed with regard to clinical differential diagnosis and potentially confounding variables\\u000a (the four T's: traumatic tap, timing, total protein and total bilirubin). The practical laboratory aspects of spectrophotometry\\u000a and automated techniques are presented in the context of

  13. Molecular mechanisms of cerebrospinal fluid production

    Microsoft Academic Search

    P. D. Brown; S. L. Davies; T. Speake; I. D. Millar

    2004-01-01

    The epithelial cells of the choroid plexuses secrete cerebrospinal fluid (CSF), by a process which involves the transport of Na+, Cl? and HCO3? from the blood to the ventricles of the brain. The unidirectional transport of ions is achieved due to the polarity of the epithelium, i.e. the ion transport proteins in the blood-facing (basolateral) membrane are different to those

  14. Pharmacokinetics of florfenicol in cerebrospinal fluid and plasma of calves.

    PubMed Central

    de Craene, B A; Deprez, P; D'Haese, E; Nelis, H J; Van den Bossche, W; De Leenheer, P

    1997-01-01

    Florfenicol, a fluorinated analog of thiamphenicol, is of great value in veterinary infectious diseases that formerly responded favorably to chloramphenicol. In view of the treatment of meningitis in calves, we studied its pharmacokinetics in the cerebrospinal fluid (CSF) and plasma of six animals. To this end, a new high-performance liquid chromatography method was developed which, unlike previous ones, uses solid-phase instead of double-phase extraction to isolate the drug. After a single intravenous dose of 20 mg/kg of body weight, a maximum concentration in CSF of 4.67 +/- 1.51 microg/ml (n = 6) was reached, with a mean residence time of 8.7 h. The decline of florfenicol in both CSF and plasma fitted a biexponential model with elimination half-lives of 13.4 and 3.2 h, respectively. Florfenicol penetrated well into CSF, as evidenced from an availability of 46% +/- 3% relative to plasma. The levels remained above the MIC for Haemophilus somnus over a 20-h period. Our results provide evidence indicating the effectiveness of florfenicol in the treatment of bacterial meningitis of calves. PMID:9303399

  15. Cerebrospinal fluid secretion by the choroid plexus.

    PubMed

    Damkier, Helle H; Brown, Peter D; Praetorius, Jeppe

    2013-10-01

    The choroid plexus epithelium is a cuboidal cell monolayer, which produces the majority of the cerebrospinal fluid. The concerted action of a variety of integral membrane proteins mediates the transepithelial movement of solutes and water across the epithelium. Secretion by the choroid plexus is characterized by an extremely high rate and by the unusual cellular polarization of well-known epithelial transport proteins. This review focuses on the specific ion and water transport by the choroid plexus cells, and then attempts to integrate the action of specific transport proteins to formulate a model of cerebrospinal fluid secretion. Significant emphasis is placed on the concept of isotonic fluid transport across epithelia, as there is still surprisingly little consensus on the basic biophysics of this phenomenon. The role of the choroid plexus in the regulation of fluid and electrolyte balance in the central nervous system is discussed, and choroid plexus dysfunctions are described in a very diverse set of clinical conditions such as aging, Alzheimer's disease, brain edema, neoplasms, and hydrocephalus. Although the choroid plexus may only have an indirect influence on the pathogenesis of these conditions, the ability to modify epithelial function may be an important component of future therapies. PMID:24137023

  16. A Case of Cerebrospinal Fluid Rhinorrhoea: A Surgical Challenge

    PubMed Central

    R, Sumitha; Hari, P M; Kumar, S Ramya; Hariprasad, R

    2013-01-01

    CEREBROSPINAL FLUID rhinorrhoea is defined as the leakage of CEREBROSPINAL FLUID through the nose due to communication between nasal cavity and Sub-arachnoid space. It occurs due to breach in 4 layers – mucosa of the nose and PNS, skull base, Duramater, Subarachnoid membrane. With the advent of nasal endoscope and advancement in technology, Endoscopic Endonasal closure of CEREBROSPINAL FLUID leak has reached tremendous heights due to exact localization and precise placement of graft. In this article, we are publishing a case report of Non-traumatic normal pressure CEREBROSPINAL FLUID leak of more than 1.5cm in size which was successfully closed Endoscopically by multilayered technique PMID:23998089

  17. Observations on an Epidemic of Cerebrospinal Meningitis in Cyprus and the Record of a Prophylactic Experiment

    PubMed Central

    Maclean, I. H.; Bevan, C. E.

    1939-01-01

    After a lapse of twenty-five years cerebrospinal meningitis appeared again in epidemic from during 1936-37. A prophylactic inoculation experiment was undertaken during the autumn of 1937, a few months before the second epidemic season was due to begin. Season 1936-37—836 cases—284 deaths. Season 1937-38 (after inoculation)—298 cases—81 deaths. Season 1938-39—122 cases—51 deaths (to end of May, 1939). During the second season conditions were suitable for the continuance of the epidemic. We do not think that we obtained a false result by inoculating on a waning epidemic. Our results are inconclusive because owing to the sharp decline in the morbidity neither control nor inoculated groups were fully at risk. But our results are good enough to recommend a further trial of prophylaxis in future epidemics. The percentage of the population inoculated is an important factor. The aim should be 100%. The experiment should aim at controlling not only the meningococcal carrier rate but also the general catarrh rate. We suggest that the rapid passage of the meningoccocus in association with an epidemic of nasopharyngeal catarrh raises the virulence of the meningococcus. As the opportunity of a second experience in the prevention of cerebrospinal meningitis by prophylactic inoculation seldom occurs to an individual, we take this chance of making recommendations for guiding future experiments. PMID:19992142

  18. CEREBROSPINAL FLUID STASIS AND ITS CLINICAL SIGNIFICANCE

    PubMed Central

    Whedon, James M.; Glassey, Donald

    2010-01-01

    We hypothesize that stasis of the cerebrospinal fluid (CSF) occurs commonly and is detrimental to health. Physiologic factors affecting the normal circulation of CSF include cardiovascular, respiratory, and vasomotor influences. The CSF maintains the electrolytic environment of the central nervous system (CNS), influences systemic acid-base balance, serves as a medium for the supply of nutrients to neuronal and glial cells, functions as a lymphatic system for the CNS by removing the waste products of cellular metabolism, and transports hormones, neurotransmitters, releasing factors, and other neuropeptides throughout the CNS. Physiologic impedance or cessation of CSF flow may occur commonly in the absence of degenerative changes or pathology and may compromise the normal physiologic functions of the CSF. CSF appears to be particularly prone to stasis within the spinal canal. CSF stasis may be associated with adverse mechanical cord tension, vertebral subluxation syndrome, reduced cranial rhythmic impulse, and restricted respiratory function. Increased sympathetic tone, facilitated spinal segments, dural tension, and decreased CSF flow have been described as closely related aspects of an overall pattern of structural and energetic dysfunction in the axial skeleton and CNS. Therapies directed at affecting CSF flow include osteopathic care (especially cranial manipulation), craniosacral therapy, chiropractic adjustment of the spine and cranium, Network Care (formerly Network Chiropractic), massage therapy (including lymphatic drainage techniques), yoga, therapeutic breathwork, and cerebrospinal fluid technique. Further investigation into the nature and causation of CSF stasis, its potential effects upon human health, and effective therapies for its correction is warranted. PMID:19472865

  19. A chronic fatigue syndrome – related proteome in human cerebrospinal fluid

    Microsoft Academic Search

    James N. Baraniuk; Begona Casado; Hilda Maibach; Daniel J. Clauw; Lewis K. Pannell; Sonja Hess S

    2005-01-01

    BACKGROUND: Chronic Fatigue Syndrome (CFS), Persian Gulf War Illness (PGI), and fibromyalgia are overlapping symptom complexes without objective markers or known pathophysiology. Neurological dysfunction is common. We assessed cerebrospinal fluid to find proteins that were differentially expressed in this CFS-spectrum of illnesses compared to control subjects. METHODS: Cerebrospinal fluid specimens from 10 CFS, 10 PGI, and 10 control subjects (50

  20. A new look at cerebrospinal fluid circulation.

    PubMed

    Brinker, Thomas; Stopa, Edward; Morrison, John; Klinge, Petra

    2014-01-01

    According to the traditional understanding of cerebrospinal fluid (CSF) physiology, the majority of CSF is produced by the choroid plexus, circulates through the ventricles, the cisterns, and the subarachnoid space to be absorbed into the blood by the arachnoid villi. This review surveys key developments leading to the traditional concept. Challenging this concept are novel insights utilizing molecular and cellular biology as well as neuroimaging, which indicate that CSF physiology may be much more complex than previously believed. The CSF circulation comprises not only a directed flow of CSF, but in addition a pulsatile to and fro movement throughout the entire brain with local fluid exchange between blood, interstitial fluid, and CSF. Astrocytes, aquaporins, and other membrane transporters are key elements in brain water and CSF homeostasis. A continuous bidirectional fluid exchange at the blood brain barrier produces flow rates, which exceed the choroidal CSF production rate by far. The CSF circulation around blood vessels penetrating from the subarachnoid space into the Virchow Robin spaces provides both a drainage pathway for the clearance of waste molecules from the brain and a site for the interaction of the systemic immune system with that of the brain. Important physiological functions, for example the regeneration of the brain during sleep, may depend on CSF circulation. PMID:24817998

  1. A new look at cerebrospinal fluid circulation

    PubMed Central

    2014-01-01

    According to the traditional understanding of cerebrospinal fluid (CSF) physiology, the majority of CSF is produced by the choroid plexus, circulates through the ventricles, the cisterns, and the subarachnoid space to be absorbed into the blood by the arachnoid villi. This review surveys key developments leading to the traditional concept. Challenging this concept are novel insights utilizing molecular and cellular biology as well as neuroimaging, which indicate that CSF physiology may be much more complex than previously believed. The CSF circulation comprises not only a directed flow of CSF, but in addition a pulsatile to and fro movement throughout the entire brain with local fluid exchange between blood, interstitial fluid, and CSF. Astrocytes, aquaporins, and other membrane transporters are key elements in brain water and CSF homeostasis. A continuous bidirectional fluid exchange at the blood brain barrier produces flow rates, which exceed the choroidal CSF production rate by far. The CSF circulation around blood vessels penetrating from the subarachnoid space into the Virchow Robin spaces provides both a drainage pathway for the clearance of waste molecules from the brain and a site for the interaction of the systemic immune system with that of the brain. Important physiological functions, for example the regeneration of the brain during sleep, may depend on CSF circulation. PMID:24817998

  2. Isolation of Acanthamoeba culbertsoni from a patient with meningitis.

    PubMed Central

    Lalitha, M K; Anandi, V; Srivastava, A; Thomas, K; Cherian, A M; Chandi, S M

    1985-01-01

    A case of amoebic meningitis, presumably primary, was encountered in the Christian Medical College Hospital, Vellore, South India, in November 1983. The patient, a 40-year-old man, had cerebrospinal fluid rhinorrhea before the meningitis developed. Acanthamoeba culbertsoni was repeatedly demonstrated in and cultured from the cerebrospinal fluid. The patient responded dramatically to a combination therapy of penicillin and chloramphenicol. Images PMID:3988911

  3. Cerebrospinal fluid biomarkers of Alzheimer's disease.

    PubMed

    Sui, Xiaojing; Liu, Jianjun; Yang, Xifei

    2014-04-01

    Alzheimer's disease (AD) is a fatal neurodegenerative disorder that takes about a decade to develop, making early diagnosis possible. Clinically, the diagnosis of AD is complicated, costly, and inaccurate, so it is urgent to find specific biomarkers. Due to its multifactorial nature, a panel of biomarkers for the multiple pathologies of AD, such as cerebral amyloidogenesis, neuronal dysfunction, synapse loss, oxidative stress, and inflammation, are most promising for accurate diagnosis. Highly sensitive and high-throughput proteomic techniques can be applied to develop a panel of novel biomarkers for AD. In this review, we discuss the metabolism and diagnostic performance of the well-established core candidate cerebrospinal fluid (CSF) biomarkers (?-amyloid, total tau, and hyperphosphorylated tau). Meanwhile, novel promising CSF biomarkers, especially those identified by proteomics, updated in the last five years are also extensively discussed. Furthermore, we provide perspectives on how biomarker discovery for AD is evolving. PMID:24733653

  4. Glycoproteomics of cerebrospinal fluid in neurodegenerative disease

    NASA Astrophysics Data System (ADS)

    Sihlbom, Carina; Davidsson, Pia; Emmett, Mark R.; Marshall, Alan G.; Nilsson, Carol L.

    2004-05-01

    Cerebrospinal fluid (CSF) from individual patients with Alzheimer's disease (AD) was separated by narrow range two-dimensional (2D) gel electrophoresis and analyzed by electrospray FT-ICR MS in this glycoproteomic study. Because several altered proteins in the comparison between AD patients and healthy controls individuals are isoforms of glycoproteins, it is important to determine if the modifying glycans are also altered. FT-ICR MS and fragmentation of glycopeptides with infrared multiphoton dissociation (IRMPD) offers abundant fragment ions through breakage at the glycosidic linkages with excellent mass accuracy, which facilitates the structural determination of the site-specific N-linked glycosylation. We present results from a structural comparison of proteins from three AD patients and three control individuals of different glycosylated isomers of [alpha]-1-antitrypsin, [beta]-trace and apolipoprotein J.

  5. Imhotep and the Discovery of Cerebrospinal Fluid

    PubMed Central

    Blomstedt, Patric

    2014-01-01

    Herbowski (2013) suggested recently the Egyptian Imhotep from the 3rd dynasty in Egypt to be the discoverer of cerebrospinal fluid. There are, however, no sources within the first 2000 years after Imhotep suggesting him to be in any way connected with the field of medicine. Over the course of three millennia Imhotep evolves into the sage who besides architecture also masters the arts of medicine, magic, astronomy, and astrology, at the same time as him being transformed from man to demi-God, and finally to a God. The identification of Imhotep as a doctor has thus little to do with facts and it is unlikely that he had anything to do with the Edwin-Smith papyrus from a much later period where CSF is first mentioned. PMID:24744920

  6. [Radioisotopic methods for studying cerebrospinal fluid shunts].

    PubMed

    Depresseux, J C; Stevenaert, A

    1976-01-01

    The article presents a general and critical review of the radio-isotopic methods for assessing the function of the surgical shunts of cerebrospinal fluid (CSF). The radio-isotope cisternography may indirectly demonstrate the function of the shunt by the postoperative modification of the eventual ventricular reflux and of the permeability of the subarachnoid spaces on the cerebral convexity. The methods of direct ventricular injection of the indicator permit a more direct assessment of the drainage, as based on a scintigraphy, or on the quantitative study of the cephalic radio-activity, or on the demonstration of radio-activityon a target-organ. The direct injection of a highly diffusible indicator in the valve allows a quantitative measurement of the flow of CSF in the shunt and brings morphological arguments for the localization of the eventual occlusion. The technical aspects of the latter method are critically discussed and illustrated by personal results. PMID:796747

  7. Characterization of individual mouse cerebrospinal fluid proteomes

    SciTech Connect

    Smith, Jeffrey S.; Angel, Thomas E.; Chavkin, Charles; Orton, Daniel J.; Moore, Ronald J.; Smith, Richard D.

    2014-03-20

    Analysis of cerebrospinal fluid (CSF) offers key insight into the status of the central nervous system. Characterization of murine CSF proteomes can provide a valuable resource for studying central nervous system injury and disease in animal models. However, the small volume of CSF in mice has thus far limited individual mouse proteome characterization. Through non-terminal CSF extractions in C57Bl/6 mice and high-resolution liquid chromatography-mass spectrometry analysis of individual murine samples, we report the most comprehensive proteome characterization of individual murine CSF to date. Utilizing stringent protein inclusion criteria that required the identification of at least two unique peptides (1% false discovery rate at the peptide level) we identified a total of 566 unique proteins, including 128 proteins from three individual CSF samples that have been previously identified in brain tissue. Our methods and analysis provide a mechanism for individual murine CSF proteome analysis.

  8. Imhotep and the discovery of cerebrospinal fluid.

    PubMed

    Blomstedt, Patric

    2014-01-01

    Herbowski (2013) suggested recently the Egyptian Imhotep from the 3rd dynasty in Egypt to be the discoverer of cerebrospinal fluid. There are, however, no sources within the first 2000 years after Imhotep suggesting him to be in any way connected with the field of medicine. Over the course of three millennia Imhotep evolves into the sage who besides architecture also masters the arts of medicine, magic, astronomy, and astrology, at the same time as him being transformed from man to demi-God, and finally to a God. The identification of Imhotep as a doctor has thus little to do with facts and it is unlikely that he had anything to do with the Edwin-Smith papyrus from a much later period where CSF is first mentioned. PMID:24744920

  9. Mirtazapine enantiomers in blood and cerebrospinal fluid.

    PubMed

    Baumann, Pierre; Jonzier-Perey, Michèle; Paus, Erik; Nikisch, Georg

    2006-01-01

    Little information exists on the concentrations of recent antidepressants and their metabolites in cerebrospinal fluid (CSF). Using a stereoselective method, we measured plasma and CSF levels of mirtazapine (MIR), N-demethylmirtazapine and 8-OH-MIR in 3 depressed patients treated with racemic MIR (45 mg/day) for 4 weeks. S-(+)-MIR is considered to be the antidepressant enantiomer, but only R-(-)-MIR reached measurable concentrations in CSF. For R-(-)-MIR, the CSF/plasma ratio varied between 0.08 and 0.31. Further studies are needed to test the hypothesis that there are possible differences in the transport mechanisms of the enantiomers of MIR at the blood-CSF barrier. PMID:17230030

  10. Cerebrospinal Fluid Proteome of Patients with Acute Lyme Disease

    SciTech Connect

    Angel, Thomas E.; Jacobs, Jon M.; Smith, Robert P.; Pasternack, Mark S.; Elias, Susan; Gritsenko, Marina A.; Shukla, Anil K.; Gilmore, Edward C.; McCarthy, Carol; Camp, David G.; Smith, Richard D.

    2012-10-05

    Acute Lyme disease results from transmission of and infection by the bacterium Borrelia burgdorferi following a tick bite. During acute infection, bacteria can disseminate to the central nervous system (CNS) leading to the development of Lyme meningitis. Here we have analyzed pooled cerebrospinal fluid (CSF) allowing for a deep view into the proteome for a cohort of patients with early-disseminated Lyme disease and CSF inflammation leading to the identification of proteins that reflect host responses, which are distinct for subjects with acute Lyme disease. Additionally, we analyzed individual patient samples and quantified changes in protein abundance employing label-free quantitative mass spectrometry based methods. The measured changes in protein abundances reflect the impact of acute Lyme disease on the CNS as presented in CSF. We have identified 89 proteins that differ significantly in abundance in patients with acute Lyme disease. A number of the differentially abundant proteins have been found to be localized to brain synapse and thus constitute important leads for better understanding of the neurological consequence of disseminated Lyme disease.

  11. Cerebrospinal fluid rhinorrhea following surgery for acoustic neurinoma. Report of two cases.

    PubMed

    Gordon, D S; Kerr, A G

    1986-04-01

    In a series of 48 patients with acoustic neurinoma removed by the suboccipital route, one patient developed cerebrospinal fluid rhinorrhea and another patient had delayed-onset meningitis. Each complication was attributed to opening the posteromedial air-cell tract in the posterior wall of the internal auditory meatus. In operations requiring removal of the posterior meatal wall, it is important to look for the air-cell tract which may not be apparent on computerized tomography. If the tract is opened the cells should be occluded by bone wax. PMID:3950753

  12. Meningitis

    MedlinePLUS

    ... news. However, it's also pretty rare. What Is Meningitis? Meningitis means inflammation of the membranes surrounding the brain ... the brain and spinal cord). People can get meningitis at any age. There are several types of ...

  13. Meningitis

    MedlinePLUS

    Meningitis is a bacterial infection of the membranes covering the brain and spinal cord (meninges). ... The most common causes of meningitis are viral infections that usually ... infections are extremely serious, and may result in death ...

  14. Meningitis

    MedlinePLUS

    ... system, infecting the meninges and causing meningitis. Continue Bacteria and Viruses Many viruses can cause viral meningitis. ... examined under a microscope to see if any bacteria, cells, or substances that indicate inflammation or infection ...

  15. Therapeutic amprenavir concentrations in cerebrospinal fluid.

    PubMed

    Croteau, David; Letendre, Scott; Best, Brookie M; Rossi, Steven S; Ellis, Ronald J; Clifford, David B; Collier, Ann C; Gelman, Benjamin B; Marra, Christina M; McArthur, Justin; McCutchan, J Allen; Morgello, Susan; Simpson, David M; Way, Lauren; Capparelli, Edmund; Grant, Igor

    2012-04-01

    Antiretrovirals that reach higher concentrations in cerebrospinal fluid (CSF) are associated with better control of HIV in CSF and possibly better neurocognitive performance. The objective of this study was to determine whether amprenavir (APV) concentrations in CSF are in the therapeutic range. Individuals were selected based on the use of regimens that included fosamprenavir (FPV), a prodrug of APV, and the availability of stored CSF and matched plasma. Total APV was measured in 119 matched CSF-plasma pairs from 75 subjects by high-performance liquid chromatography (HPLC) (plasma) or liquid chromatography tandem mass spectrometry (LC/MS/MS) (CSF). Concentrations were compared to the 50% inhibitory concentration (IC??) for wild-type HIV (5.6 ng/ml). Subjects were predominantly middle-aged (median 44 years) white (57%) men (78%) with AIDS (77%). APV was detected in all but 4 CSF specimens, with a median concentration of 24.8 ng/ml (interquartile range [IQR], 16.2 to 44.0). The median CSF-to-plasma ratio was 0.012 (IQR, 0.008 to 0.018). CSF concentrations correlated with plasma concentrations (rho = 0.61; P < 0.0001) and with postdose sampling interval (rho = -0.29; P = 0.0019). APV concentrations in CSF exceeded the median IC?? for wild-type HIV in more than 97% of CSF specimens with detectable APV by a median of 4.4-fold (IQR, 2.9 to 7.9). We conclude that administration of fosamprenavir should contribute to control of HIV replication in the central nervous system (CNS) as a component of effective antiretroviral regimens. PMID:22290964

  16. Quantitative proteomics of delirium cerebrospinal fluid

    PubMed Central

    Poljak, A; Hill, M; Hall, R J; MacLullich, A M; Raftery, M J; Tai, J; Yan, S; Caplan, G A

    2014-01-01

    Delirium is a common cause and complication of hospitalization in older people, being associated with higher risk of future dementia and progression of existing dementia. However relatively little data are available on which biochemical pathways are dysregulated in the brain during delirium episodes, whether there are protein expression changes common among delirium subjects and whether there are any changes which correlate with the severity of delirium. We now present the first proteomic analysis of delirium cerebrospinal fluid (CSF), and one of few studies exploring protein expression changes in delirium. More than 270 proteins were identified in two delirium cohorts, 16 of which were dysregulated in at least 8 of 17 delirium subjects compared with a mild Alzheimer's disease neurological control group, and 31 proteins were significantly correlated with cognitive scores (mini-mental state exam and acute physiology and chronic health evaluation III). Bioinformatics analyses revealed expression changes in several protein family groups, including apolipoproteins, secretogranins/chromogranins, clotting/fibrinolysis factors, serine protease inhibitors and acute-phase response elements. These data not only provide confirmatory evidence that the inflammatory response is a component of delirium, but also reveal dysregulation of protein expression in a number of novel and unexpected clusters of proteins, in particular the granins. Another surprising outcome of this work is the level of similarity of CSF protein profiles in delirium patients, given the diversity of causes of this syndrome. These data provide additional elements for consideration in the pathophysiology of delirium as well as potential biomarker candidates for delirium diagnosis. PMID:25369144

  17. Cerebrospinal fluid concentrations of antituberculosis agents in adults and children.

    PubMed

    Donald, P R

    2010-09-01

    Tuberculous meningitis (TBM) causes a devastating morbidity and mortality in adults and children. Even in patients presenting at an early stage of disease, deterioration may occur despite apparently adequate therapy. The literature relating to cerebrospinal fluid penetration of antituberculosis agents is reviewed. Amongst the essential antituberculosis agents isoniazid has the best CSF pharmacokinetics reaching peak concentrations (C(max)) only slightly less than in blood. Pyrazinamide also has good CSF penetration and in children receiving dosages of 40 mg/kg the CSF C(max) exceeds the proposed minimal inhibitory concentration of 20 ?g/ml. Streptomycin other aminoglycosides and ethambutol have poor CSF penetration and cannot be agents of first choice for TBM treatment. Rifampicin at dosages used in adults seldom reaches CSF concentrations exceeding MIC, but does so more frequently in children when dosages of up to 20 mg/kg are used. The non-essential agents ethionamide, the fluoroquinolones, with the exception of ciprofloxacin, and cycloserine (terizadone) have relatively good CSF penetration and are recommended for TBM treatment. The dosages of the essential agents recommended for the treatment of TBM in children are INH 10 mg/kg (range 6-15 mg/kg bodyweight), rifampicin 15 mg/kg (range 10-20 mg/kg), pyrazinamide 35 mg/kg (range 30-40 mg/kg), ethambutol 20 mg/kg (range 15-25 mg/kg) and streptomycin 15 mg/kg (range 12-18 mg/kg). Amongst second-line agents ofloxacin, levofloxacin and moxifloxacin should be used in dosages of 15-20 mg/kg, ethionamide 20 mg/kg in a single dose, if tolerated, and for cycloserine (terizadone) 15 mg/kg. Antituberculous chemotherapy should be started as soon as the diagnosis of TBM is considered. PMID:20709598

  18. New cephalosporins cefotaxime, cefpimizole, BMY 28142, and HR 810 in experimental pneumococcal meningitis in rabbits.

    PubMed Central

    Täuber, M G; Hackbarth, C J; Scott, K G; Rusnak, M G; Sande, M A

    1985-01-01

    Four new cephalosporins, cefotaxime, cefpimizole (U 63196E), BMY 28142, and HR 810 were evaluated in experimental pneumococcal meningitis. Cefotaxime penetrated only moderately into the cerebrospinal fluid of rabbits with meningitis, whereas cefpimizole, BMY 28142, and HR 810 all exhibited unusually good penetration. The bactericidal activity in infected cerebrospinal fluid was comparable for the four drugs. PMID:3838872

  19. C-reactive protein is useful in distinguishing Gram stain–negative bacterial meningitis from viral meningitis in children

    Microsoft Academic Search

    Päivi Sormunen; Markku J. T. Kallio; Terhi Kilpi; Heikki Peltola

    1999-01-01

    Objective: To clarify to what extent Gram stain–negative bacterial meningitis can be distinguished from viral meningitis by assessment of cerebrospinal fluid (CSF) and blood indices and serum C-reactive protein (CRP) in children over 3 months of age. Design: Common CSF indices, blood leukocyte counts, and serum CRP values were compared between patients with bacterial meningitis who had a positive CSF

  20. Monoamine metabolites in human cerebrospinal fluid. HPLC/ED method.

    PubMed

    Mena, M A; Aguado, E G; de Yebenes, J G

    1984-04-01

    Catecholamines and indolealkylamines are of clinical interest in neurological and psychiatric disorders. We measured 3-methoxy-DOPA, 3-methoxy-4-hydroxyphenylglycol, dihydroxyphenylacetic acid, tryptophan, 5-hydroxyindoleacetic acid and homovanillic acid in human cerebrospinal fluid with a simple, sensitive , inexpensive, rapid and accurate procedure using high performance liquid chromatography coupled to an electrochemical detector. Patients with Parkinson's disease have a decrement in homovanillic acid that is reversed by treatment with L-3,4-dihydroxyphenylalanine. After this medication, 3-methoxy-DOPA is measurable in cerebrospinal fluid. Patients with depression show a decrease in serotonin turnover expressed by diminished 5-hydroxyindoleacetic acid content in cerebrospinal fluid. Depressed patients also show low levels of tryptophan. Monoamine metabolites are augmented in patients with subarachnoid hemorrhage. PMID:6204498

  1. Aztreonam therapy in experimental meningitis due to Haemophilus influenzae type b and Escherichia coli K1.

    PubMed Central

    McCracken, G H; Sakata, Y; Olsen, K D

    1985-01-01

    The penetration of aztreonam into cerebrospinal fluid was 7 to 15% and 9 to 25%, respectively, in experimental Haemophilus influenzae type b and Escherichia coli K1 meningitis. Aztreonam was effective in reducing the number of organisms in cerebrospinal fluid after single-dose and continuous infusion administration, and the median bactericidal titers in cerebrospinal fluid were 1:32 against both meningeal pathogens. PMID:3890733

  2. Application of transport phenomena analysis technique to cerebrospinal fluid.

    PubMed

    Lam, C H; Hansen, E A; Hall, W A; Hubel, A

    2013-12-01

    The study of hydrocephalus and the modeling of cerebrospinal fluid flow have proceeded in the past using mathematical analysis that was very capable of prediction phenomenonologically but not well in physiologic parameters. In this paper, the basis of fluid dynamics at the physiologic state is explained using first established equations of transport phenomenon. Then, microscopic and molecular level techniques of modeling are described using porous media theory and chemical kinetic theory and then applied to cerebrospinal fluid (CSF) dynamics. Using techniques of transport analysis allows the field of cerebrospinal fluid dynamics to approach the level of sophistication of urine and blood transport. Concepts such as intracellular and intercellular pathways, compartmentalization, and tortuosity are associated with quantifiable parameters that are relevant to the anatomy and physiology of cerebrospinal fluid transport. The engineering field of transport phenomenon is rich and steeped in architectural, aeronautical, nautical, and more recently biological history. This paper summarizes and reviews the approaches that have been taken in the field of engineering and applies it to CSF flow. PMID:24091435

  3. Traumatic cerebrospinal fluid leakage: risk factors and the use of prophylactic antibiotics.

    PubMed

    Choi, D; Spann, R

    1996-12-01

    Cerebrospinal fluid (CSF) leakage following head trauma is often difficult to diagnose, but is of considerable importance in view of the possibility of fistula formation and meningitis. It is unclear whether specific clinical or radiological signs point to an increased risk of CSF leakage. Previous studies have been largely anecdotal and uncontrolled, leading us to perform a retrospective control study comparing the clinical and radiological features of patients with overt CSF leakage, and those without. Of the 293 patients studied, 115 had clinical CSF leakage and 170 did not, with incomplete documentation in eight patients. The group with CSF rhinorrhoea had significantly greater incidence of periorbital haematoma (chi square = 8.642). This suggests that patients with head injuries and features of periorbital haematoma are at greater risk of unobserved dural tear and delayed CSF leakage. Frontal and ethmoid fractures in particular were also associated with CSF leakage (chi square = 5.46). The use of prophylactic antibiotics was studied. There was a significantly greater incidence of meningitis in the group which received prophylactic antibiotics (p = 0.024). There was no significant difference in the incidence of meningitis in those patients with CSF fistulae treated by surgical or conservative methods. PMID:9115653

  4. [Angiostrongylosis or eosinophilic meningitis].

    PubMed

    Bourée, Patrice; Dumazedier, Déborah; Dahane, Naïma

    2010-04-20

    Eosinophilic meningitis, or angiostrongyliasis, is a common disease in Asia, in the Caribbean and in the Pacific islands. It is caused by a rat lungworm Angiostrongylus cantonensis. Infection occurs by consumption of raw or undercooked snails. Diagnosis is based on epidemiological criteria, clinical manifestations, elevated count of eosinophils in the cerebrospinal fluid and serological tests. Treatment is symptomatic and supportive. PMID:20465114

  5. More Than the Brain's Drain: Does Cerebrospinal Fluid Help the Brain Convey Messages?

    ERIC Educational Resources Information Center

    Travis, John

    1999-01-01

    Examines the role of cerebrospinal fluid (CSF), a clear, colorless liquid that constantly bathes the brain and spinal cord. Scientists argue that cerebrospinal fluid carries important signals for sleep, appetite, and sex. Evaluates past and current research documenting the purpose of cerebrospinal fluid in the brain. (CCM)

  6. Increased cerebrospinal fluid tau in patients with Alzheimer's disease

    Microsoft Academic Search

    Malene Jensen; Hans Basun; Lars Lannfelt

    1995-01-01

    One of the pathological features in Alzheimer's disease (AD) is neurofibrillary tangles in the brain. The main constituent of tangles is the microtubuli-associated protein tau in a hyperphosphorylated state. Tau is also released into cerebrospinal fluid (CSF), and in this study we have used an enzyme linked immunosorbent assay to measure tau in CSF from AD and control cases. Our

  7. Cerebrospinal fluid volume analysis for hydrocephalus diagnosis and clinical research

    E-print Network

    Paris-Sud XI, Université de

    with various types of hydrocephalus in [3, 4], whereas it is limited to normal pressure hydrocephalus, iCerebrospinal fluid volume analysis for hydrocephalus diagnosis and clinical research Alain Lebreta in range [0.63, 4.61] for hydrocephalus patients. This indicates that a robust distinction between

  8. Elevated cerebrospinal fluid pressure in patients with Alzheimer's disease

    Microsoft Academic Search

    Gerald Silverberg; Martha Mayo; Thomas Saul; Jere Fellmann; Dawn McGuire

    2006-01-01

    BACKGROUND: Abnormalities in cerebrospinal fluid (CSF) production and turnover, seen in normal pressure hydrocephalus (NPH) and in Alzheimer's disease (AD), may be an important cause of amyloid retention in the brain and may relate the two diseases. There is a high incidence of AD pathology in patients being shunted for NPH, the AD-NPH syndrome. We now report elevated CSF pressure

  9. Transnasal endoscopic treatment of cerebrospinal fluid leak: 17 years’ experience

    PubMed Central

    Presutti, L; Mattioli, F; Villari, D; Marchioni, D; Alicandri-Ciufelli, M

    2009-01-01

    Summary Aim of this report is to describe the long-term results of endoscopic endonasal repair of cerebrospinal fluid leak using a septal mucoperichondrial graft. A case series of 52 patients operated for cerebrospinal fluid rhinorrhea between 1990 and 2006 is presented. All patients underwent surgical treatment for endoscopic endonasal closure of a cerebrospinal fluid leak using a septal mucoperichondrial graft. No lumbar drain and fluorescein tests were used. The intra-operative localization of the fistula was aided by Valsalva’s manoeuvre by the anaesthetist. The success rate, after the first attempt, was 88.5% (46/52 patients); for the remaining 11.5% (6/52 patients), a second attempt was necessary which proved successful in 5 cases, raising the overall success rate to 98.1% (51/52 patients). Relapse occurred in only one case (1.9%), after the second attempt. In conclusion, a free mucoperichondrial graft offered good results for cerebrospinal fluid leak repair. In the Authors’ experience, a high success rate can be achieved without the use of intrathecal fluorescein and lumbar drain. PMID:20161876

  10. ORIGINAL ARTICLES Cerebrospinal Fluid Corticotropin-Releasing Hormone

    E-print Network

    Wisconsin at Madison, University of

    . Shelton, and Richard J. Davidson Background: Asymmetric patterns of frontal brain activ- ity and brain right frontal asymmetric brain electrical activity have high levels of trait-like fearful behavior and increased plasma cortisol concentrations. Methods: In this study we assessed cerebrospinal fluid (CSF) CRH

  11. Postoperative cerebrospinal fluid leak after septoplasty: A potential complication of occult anterior skull base encephalocele

    PubMed Central

    Soni, Resha S.; Choudhry, Osamah J.; Liu, James K.

    2013-01-01

    Postoperative cerebrospinal fluid (CSF) rhinorrhea after septoplasty is a known entity resulting from errors in surgical technique and improper handling of the perpendicular plate of the ethmoid bone. When these occur, urgent management is necessary to prevent deleterious sequelae such as meningitis, intracranial abscess, and pneumocephalus. Encephaloceles are rare occurrences characterized by herniation of intracranial contents through a skull base defect that can predispose patients to CSF rhinorrhea. In this report, we present a case of CSF rhinorrhea occurring 2 weeks after septoplasty likely from manipulation of an occult anterior skull base encephalocele. To our knowledge, no previous similar case has been reported in the literature. Otolaryngologists should be aware of the possibility of occult encephaloceles while performing septoplasties because minimal manipulation of these entities may potentially result in postoperative CSF leakage. PMID:23772326

  12. A new look at cerebrospinal fluid movement

    PubMed Central

    2014-01-01

    Brinker et al. extensively reviewed recent findings about CSF circulation in a recent article: “A new look at cerebrospinal circulation”, but did not analyze some important available data in sufficient detail. For example, our findings as well as some clinical data and experimental results obtained from different animal species, do not support unidirectional CSF circulation but strongly suggest that there are cardiac cycle-dependent systolic-diastolic to-and-fro cranio-spinal CSF movements. These are based on: a) physiological oscillations of arterial and venous blood during cranio-spinal blood circulation; b) respiratory activity, and c) body activity and posture. That kind of complex CSF movement could explain the observed distribution of many different substances in all directions along the CSF system and within central nervous system tissue. It seems that efflux transport systems at capillary endothelium may be more important for brain homeostasis than the removal of metabolites by CSF flow. Thus, when discussing the CSF dynamics we suggest that a more appropriate term would be CSF movement rather than CSF circulation. PMID:25089184

  13. Citrobacter sedlakii meningitis and brain abscess in a premature infant.

    PubMed Central

    Dyer, J; Hayani, K C; Janda, W M; Schreckenberger, P C

    1997-01-01

    Citrobacter sedlakii was isolated from blood and cerebrospinal fluid cultures of a 5-day-old premature infant with sepsis, meningitis, and brain abscess. This newly described organism was difficult to identify due to discrepancies between the Vitek and API 20E identification systems. To our knowledge, this is the first report of the isolation of C. sedlakii from cerebrospinal fluid. PMID:9316937

  14. Concentration gradients for monoamine metabolites in lumbar cerebrospinal fluid

    Microsoft Academic Search

    K. Blennow; A. Wallin; C. G. Gottfries; J.-E. Månsson; L. Svennerholm

    1993-01-01

    Summary  Concentration gradients in lumbar cerebrospinal fluid (CSF) for the monoamine metabolites homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA) and 4-hydroxy-3-methoxyphenylglycol (HMPG) were studied in 9 healthy controls and 47 neuropsychiatric patients without diseases causing disturbed CSF circulation. In a serial sampling of the first 24 ml of CSF, steep concentration gradients between the first (0–4 th ml) and last (21th–24th ml)

  15. Alzheimer's disease: paired helical filament immunoreactivity in cerebrospinal fluid

    Microsoft Academic Search

    G. P. Wang; K. Iqbal; G. Bucht; B. Winblad; H. M. Wisniewski; I. Grundke-Iqbal

    1991-01-01

    A competitive enzyme-linked immunosorbent assay with high sensitivity has been developed for measuring ubiquitin reactivity of paired helical filaments (PHF). Using the assay, ubiquitin immunoreactivity was estimated in the cerebrospinal fluid (CSF) of 44 patients who had been clinically diagnosed as having Alzheimer's disease (AD) and of 38 control patients, including 20 neurological cases. Monoclonal antibody (mAb) 5–25 to isolated

  16. Nitrite and nitrate levels in cerebrospinal fluid of normal subjects

    Microsoft Academic Search

    L. Zecca; M. Rosati; R. Renella; M. Galimberti; A. Ambrosini; R. G. Fariello

    1998-01-01

    Summary.   In order to evaluate the involvement of nitric oxide in neurologic disorders it is important to generate controlled values\\u000a of its metabolites nitrite and nitrate in human cerebrospinal fluid (CSF). Samples of CSF obtained from 14 patients without\\u000a neurologic diseases were analysed for nitrite and nitrate concentration by reverse phase chromatography with ultraviolet (UV)\\u000a detection. For comparison, the levels

  17. Cerebrospinal fluid proteins and cells in normal-pressure hydrocephalus

    Microsoft Academic Search

    C. Wikkelsø; C. Blomstrand

    1982-01-01

    Summary  A total of 21 patients with normal-pressure hydrocephalus were examined. Cerebrospinal fluid (CSF) was collected before and\\u000a after operation with a ventriculoperitoneal shunt. A slight plasma-like protein pattern indicating a blood-brain barrier (BBB)\\u000a dysfunction was seen in 38% of the patients before operation. No characteristic changes could be found in the “CSF-specific”\\u000a protein fraction. After the shunt operation 65% of

  18. Cerebrospinal Fluid Flow in the Normal and Hydrocephalic Human Brain

    Microsoft Academic Search

    Andreas A. Linninger; Michalis Xenos; David C. Zhu; MahadevaBharath R. Somayaji; Srinivasa Kondapalli; Richard D. Penn

    2007-01-01

    Advances in magnetic resonance (MR) imaging techniques enable the accurate measurements of cerebrospinal fluid (CSF) flow in the human brain. In addition, image reconstruction tools facilitate the collection of patient-specific brain geometry data such as the exact dimensions of the ventricular and subarachnoidal spaces (SAS) as well as the computer-aided reconstruction of the CSF-filled spaces. The solution of the conservation

  19. Cerebrospinal fluid involvement in acute promyelocytic leukaemia at presentation.

    PubMed

    Mishra, Jyoti; Gupta, Mayank

    2015-01-01

    In acute promyelocytic leukaemia (APL), extramedullary disease (EMD) is rare but can occur in those who relapse following therapy. Although the most common site of EMD in APL is central nervous system (CNS) and skin, CNS involvement in recently diagnosed patients with APL is very rare and rarely described. We report cerebrospinal fluid involvement in a case of APL, on day 3 of induction therapy. PMID:25754165

  20. [Haemophilus influenzae purulent meningitis in adults: looking for a predisposing factor].

    PubMed

    Boukadida, Jalel; Hannachi, Neila

    2002-05-01

    We bring back an adult case of purulent meningitis to Haemophilus influenzae. We insist on the particular aspects of the host of this meningitis type at the adult. These aspects must be searched every time that Haemophilus influenzae is isolated in cerebrospinal fluid in adult's meningitis. PMID:12534035

  1. Idiopathic normal-pressure hydrocephalus, cerebrospinal fluid biomarkers, and the cerebrospinal fluid tap test.

    PubMed

    Kang, Kyunghun; Ko, Pan-Woo; Jin, Myungwon; Suk, Kyoungho; Lee, Ho-Won

    2014-08-01

    Cerebrospinal fluid (CSF) biomarkers, including soluble amyloid ?-42 (A?-42) and phosphorylated-tau (P-tau), reflect core pathophysiological features of Alzheimer's disease (AD). AD is frequently a concomitant pathology in older patients with idiopathic normal-pressure hydrocephalus (iNPH), and somewhat similar altered CSF dynamics exist in both AD and iNPH. We therefore investigated relationships between lumbar CSF biomarkers A?-42 and P-tau and clinical parameters in iNPH patients, along with differences in these biomarkers between CSF tap test (CSFTT) responders and non-responders. Thirty-one iNPH patients (14 CSFTT responders and 17 CSFTT non-responders) were included in the final analysis. We found lower CSF A?-42 correlated with poor cognitive performance (r=0.687, p<0.001 for Korean Mini Mental State Examination; r=0.568, p=0.001 for Frontal Assessment Battery; r=-0.439, p=0.014 for iNPH grading scale [iNPHGS] cognitive score; r=-0.588, p=0.001 for Clinical Dementia Rating Scale), and lower CSF P-tau correlated with gait dysfunction (r=-0.624, p<0.001 for Timed Up and Go Test; r=-0.652, p<0.001 for 10meter walking test; r=-0.578, p=0.001 for Gait Status Scale; r=-0.543, p=0.002 for iNPHGS gait score). In subgroup analysis, CSF P-tau/A?-42 ratios were significantly higher in CSFTT non-responders compared to responders (p=0.027). Two conjectures are suggested. One, CSF biomarkers may play different and characteristic roles in relation to different iNPH symptoms such as cognition and gait. Two, comorbid AD pathology in iNPH patients may affect the response to the CSFTT. Larger studies using combinations of other biomarkers associated with AD would be necessary to evaluate these hypotheses. PMID:24836892

  2. Survival of Trypanosoma brucei brucei in cerebrospinal fluid.

    PubMed

    Pentreath, V W; Owolabi, A O; Doua, F

    1992-02-01

    Different compositions of artificial cerebrospinal fluid (CSF) and the CSF from sleeping sickness patients both with and without late-stage [i.e. central nervous system (CNS)] involvement were evaluated for their abilities to support survival of Trypanosoma brucei brucei. Artificial CSF, containing the major electrolytes, amino acids and carbohydrate components of healthy fluid, was equivalent to the CSF from patients without CNS involvement (survival time 20 hours). Normal CSF does not therefore contain substances which deter the parasite. The CSF from the late-stage patients did not support survival for longer than 10 hours, probably because it contained increased numbers of lymphocytes and antibodies. PMID:1616393

  3. Routine Testing for Anaerobic Bacteria in Cerebrospinal Fluid Cultures Improves Recovery of Clinically Significant Pathogens

    PubMed Central

    Pittman, Meredith E.; Thomas, Benjamin S.; Wallace, Meghan A.; Weber, Carol J.

    2014-01-01

    In North America, the widespread use of vaccines targeting Haemophilus influenzae type b and Streptococcus pneumoniae have dramatically altered the epidemiology of bacterial meningitis, while the methodology for culturing cerebrospinal fluid (CSF) specimens has remained largely unchanged. The aims of this study were 2-fold: to document the current epidemiology of bacterial meningitis at a tertiary care medical center and to assess the clinical utility of routinely querying for anaerobes in CSF cultures. To that end, we assessed CSF cultures submitted over a 2-year period. A brucella blood agar (BBA) plate, incubated anaerobically for 5 days, was included in the culture procedure for all CSF specimens during the second year of evaluation. In the pre- and postimplementation years, 2,353 and 2,302 CSF specimens were cultured, with 49 and 99 patients having positive culture results, respectively. The clinical and laboratory data for patients with positive cultures were reviewed. Anaerobic bacteria were isolated in the CSF samples from 33 patients post-BBA compared to two patients pre-BBA (P = 0.01). The anaerobic isolates included Bacteroides thetaiotaomicron (n = 1), Propionibacterium species (n = 15), and Propionibacterium acnes (n = 19) isolates; all of these isolates were recovered on the BBA. Eight of the 35 patients from whom anaerobic organisms were isolated received antimicrobial therapy. Although six of these patients had central nervous system hardware, two patients did not have a history of a neurosurgical procedure and had community-acquired anaerobic bacterial meningitis. This study demonstrates that the simple addition of an anaerobically incubated BBA to the culture of CSF specimens enhances the recovery of clinically significant anaerobic pathogens. PMID:24622102

  4. Cerebrospinal fluid eosinophilia associated with intraventricular shunts.

    PubMed

    Bezerra, Sofia; Frigeri, Thomas More; Severo, Carlos Marcelo; Santana, João Carlos Batista; Graeff-Teixeira, Carlos

    2011-06-01

    CSF eosinophilia (CSF-eo) is uncommon and is usually caused by helminthic infections. However, it has also been found in ?30% of patients experiencing intraventricular shunt malfunctions. We present a case report and review the conditions associated with CSF-eo and their prophylaxis. An 8 year-old boy with tetraventricular hydrocephalus has had several shunt malfunctions over the last three years. During hospitalization in January 2009 for shunt revision, a transient 30% eosinophilia was detected in his cerebral spinal fluid (CSF) concomitant with Staphylococcus epidermidis infection and long term vancomycin administration. After several shunt replacements and antibiotic treatment, CSF-eo eventually disappeared with good overall clinical response. CSF-eo is a transient and focal event mainly associated with infection, reactions to foreign substances, particles or blood, or obstruction of tubing by normal or fibro-granulomatous tissues. Infection associated with CSF-eo is usually caused by S. epidermidis and Propioniumbacterium acnes. In addition to infection, allergy to silicone and other foreign materials may also be a cause of CSF-eo. We review the diversity of conditions and proposed mechanisms associated with CSF-eo, as well as recommendations for the care of patients with shunts. Detection of CSF-eo has been shown to be a useful indicator of shunt malfunction. As such, it provides physicians with an indicator of a hypersensitivity reaction that is underway or the need to identify bacterial infection. We also highlight the need for improved biocompatibility of shunt hardware and describe strategies to avoid conditions leading to shunt malfunction. PMID:21492998

  5. Intracranial fat migration: A newly described complication of autologous fat repair of a cerebrospinal fluid leak following supracerebellar infratentorial approach

    PubMed Central

    Ludwig, Cassie A.; Aujla, Parvir; Moreno, Mario; Veeravagu, Anand; Li, Gordon

    2014-01-01

    Introduction Intracranial fat migration following autologous fat graft and placement of a lumbar drain for cerebrospinal fluid leak after pineal cyst resection surgery has not been previously reported. Case presentation The authors present a case of a 39-year-old male with a history of headaches who presented for removal of a pineal cyst from the pineal region. He subsequently experienced cerebrospinal fluid leak and postoperative Escherichia coli (E. Coli) wound infection, and meningitis, which were treated initially with wound washout and antibiotics in addition to bone removal and primary repair with primary suture-closure of the durotomy. A lumbar drain was left in place. The cerebrospinal fluid leak returned two weeks following removal of the lumbar drain; therefore, autologous fat graft repair and lumbar drain placement were performed. Three days later, the patient began experiencing right homonymous hemianopia and was found via computed tomography and magnetic resonance imaging to have autologous fat in the infra? and supratentorial space, including intraparenchymal and subarachnoid spread. Symptoms began to resolve with supportive care over 48?hours and had almost fully resolved within one week. Discussion This is the first known report of a patient with an autologous fat graft entering the subarachnoid space, intraparenchymal space, and ventricles following fat graft and lumbar drainage. Conclusion This case highlights the importance of monitoring for complications of lumbar drain placement. PMID:25557086

  6. Keeping an open mind about meningitis: a case report of carcinomatous meningitis.

    PubMed

    Walkty, Andrew; Abbott, Burton; Swirsky, Neil; Safneck, Janice; Embil, John M

    2011-09-01

    Carcinomatous meningitis is defined as leptomeningeal infiltration by malignant cells. A case of carcinomatous meningitis, originally diagnosed as viral meningitis, is presented here to highlight the importance of maintaining a broad differential diagnosis in patients with evidence of meningeal irritation. Clinical and laboratory clues that suggest a diagnosis of carcinomatous meningitis in a patient with meningeal irritation include the presence and type of underlying malignancy (more common with breast cancer, lung cancer, and melanoma), absence of fever, presence of radicular pain, evidence of both cranial and spinal involvement, consistent cerebrospinal fluid (CSF) findings (increased opening pressure, elevated protein concentration, decreased glucose, increased white cell count), and supportive neuroimaging. Diagnosis is based on positive CSF cytology results, which may require multiple lumbar puncture procedures to obtain. For patients with a known primary malignancy who present to the emergency department with symptoms and/or signs of meningeal irritation, carcinomatous meningitis should be included in the differential diagnosis. PMID:21955418

  7. Evaluation of cerebrospinal fluid in asymptomatic late syphilis.

    PubMed

    Lee, C T; Cheong, W K; Thirumoorthy, T; Sng, E H

    1989-11-01

    A prospective study of the cerebrospinal fluid (CSF) of 49 previously untreated patients with asymptomatic late syphilis of more than two year's duration was conducted. The sera of all patients had reactive fluorescent treponemal antibody absorption (FTA-Abs) tests or Treponema pallidum haemagglutination tests (TPHA), and reactive or non-reactive Venereal Disease Research Laboratory (VDRL) tests. Five (10%) patients had abnormal CSF findings; these included elevated protein in four of 49 and pleocytosis in three of 49. Asymptomatic neurosyphilis, diagnosed on the basis of a reactive VDRL test of the CSF, was present in one (2%) of 49 patients. PMID:2624418

  8. Clinical features and prognostic factors in adults with bacterial meningitis

    Microsoft Academic Search

    Diederik van de Beek; Jan de Gans; Lodewijk Spanjaard; Martijn Weisfelt; Johannes B. Reitsma; Marinus Vermeulen

    2004-01-01

    background We conducted a nationwide study in the Netherlands to determine clinical features and prognostic factors in adults with community-acquired acute bacterial meningitis. methods From October 1998 to April 2002, all Dutch patients with community-acquired acute bacterial meningitis, confirmed by cerebrospinal fluid cultures, were prospectively eval- uated. All patients underwent a neurologic examination on admission and at discharge, and outcomes

  9. Clinical Evaluation of a Loop-Mediated Isothermal Amplification (LAMP) Assay for Rapid Detection of Neisseria meningitidis in Cerebrospinal Fluid

    PubMed Central

    Kilgore, Paul E.; Kim, Soon Ae; Takahashi, Hideyuki; Ohnishi, Makoto; Anh, Dang Duc; Dong, Bai Qing; Kim, Jung Soo; Tomono, Jun; Miyamoto, Shigehiko; Notomi, Tsugunori; Kim, Dong Wook; Seki, Mitsuko

    2015-01-01

    Background Neisseria meningitidis (Nm) is a leading causative agent of bacterial meningitis in humans. Traditionally, meningococcal meningitis has been diagnosed by bacterial culture. However, isolation of bacteria from patients’ cerebrospinal fluid (CSF) is time consuming and sometimes yields negative results. Recently, polymerase chain reaction (PCR)-based diagnostic methods of detecting Nm have been considered the gold standard because of their superior sensitivity and specificity compared with culture. In this study, we developed a loop-mediated isothermal amplification (LAMP) method and evaluated its ability to detect Nm in cerebrospinal fluid (CSF). Methodology/Principal Findings We developed a meningococcal LAMP assay (Nm LAMP) that targets the ctrA gene. The primer specificity was validated using 16 strains of N. meningitidis (serogroup A, B, C, D, 29-E, W-135, X, Y, and Z) and 19 non-N. meningitidis species. Within 60 min, the Nm LAMP detected down to ten copies per reaction with sensitivity 1000-fold more than that of conventional PCR. The LAMP assays were evaluated using a set of 1574 randomly selected CSF specimens from children with suspected meningitis collected between 1998 and 2002 in Vietnam, China, and Korea. The LAMP method was shown to be more sensitive than PCR methods for CSF samples (31 CSF samples were positive by LAMP vs. 25 by PCR). The detection rate of the LAMP method was substantially higher than that of the PCR method. In a comparative analysis of the PCR and LAMP assays, the clinical sensitivity, specificity, positive predictive value, and negative predictive value of the LAMP assay were 100%, 99.6%, 80.6%, and 100%, respectively. Conclusions/Significance Compared to PCR, LAMP detected Nm with higher analytical and clinical sensitivity. This sensitive and specific LAMP method offers significant advantages for screening patients on a population basis and for diagnosis in clinical settings. PMID:25853422

  10. The usefulness of cerebrospinal fluid tests for neurosyphilis.

    PubMed

    Russouw, H G; Roberts, M C; Emsley, R A; Joubert, J J

    1994-10-01

    To determine the usefulness of cerebrospinal fluid (CSF) tests for syphilis at a large academic hospital, clinical and laboratory data on 644 patients in whom such testing was requested over a 12-month period were analysed. In 198 cases (31%) the Treponema pallidum haemagglutination (TPHA) screening test could not be performed because of insufficient fluid. Thirty-eight of the remaining patients were diagnosed as having active neurosyphilis. Examination of 22 files of patients who had a positive TPHA and fluorescent treponemal antibody absorption (FTA-Abs) test together with a negative CSF Venereal Disease Research Laboratory (VDRL) test revealed that other CSF measures indicating disease activity (CSF protein, cells or IgG index) were not utilised optimally. In 10 (45%) of these patients neurosyphilis was not diagnosed despite either abnormal or incomplete CSF biochemical analysis, indicating that if the CSF VDRL is used as the sole marker for disease activity, some cases of neurosyphilis are likely to be missed. PMID:7839257

  11. The function and structure of the cerebrospinal fluid outflow system

    PubMed Central

    2010-01-01

    This review traces the development of our understanding of the anatomy and physiological properties of the two systems responsible for the drainage of cerebrospinal fluid (CSF) into the systemic circulation. The roles of the cranial and spinal arachnoid villi (AV) and the lymphatic outflow systems are evaluated as to the dominance of one over the other in various species and degree of animal maturation. The functional capabilities of the total CSF drainage system are presented, with evidence that the duality of the system is supported by the changes in fluid outflow dynamics in human and sub-human primates in hydrocephalus. The review also reconciles the relative importance and alterations of each of the outflow systems in a variety of clinical pathological conditions. PMID:20565964

  12. More advanced Alzheimer's disease may be associated with a decrease in cerebrospinal fluid pressure

    Microsoft Academic Search

    Peter Wostyn; Kurt Audenaert; Peter Paul De Deyn

    2009-01-01

    In a recent article, elevated cerebrospinal fluid pressure (CSFP) consistent with very early normal pressure hydrocephalus (NPH), was found in a small subset of Alzheimer's disease (AD) patients (possible AD-NPH hybrids) enrolled in a clinical trial for chronic low-flow cerebrospinal fluid drainage. Also in the same study, was another interesting finding that merits further discussion: a substantial proportion of AD

  13. High Blood Pressure Effects on the Blood to Cerebrospinal Fluid Barrier and Cerebrospinal Fluid Protein Composition: A Two-Dimensional Electrophoresis Study in Spontaneously Hypertensive Rats

    PubMed Central

    González-Marrero, Ibrahim; Castañeyra-Ruiz, Leandro; González-Toledo, Juan M.; Castañeyra-Ruiz, Agustín; de Paz-Carmona, Hector; Castro, Rafael; Hernandez-Fernaud, Juan R.; Castañeyra-Perdomo, Agustín; Carmona-Calero, Emilia M.

    2013-01-01

    The aim of the present work is to analyze the cerebrospinal fluid proteomic profile, trying to find possible biomarkers of the effects of hypertension of the blood to CSF barrier disruption in the brain and their participation in the cholesterol and ?-amyloid metabolism and inflammatory processes. Cerebrospinal fluid (CSF) is a system linked to the brain and its composition can be altered not only by encephalic disorder, but also by systemic diseases such as arterial hypertension, which produces alterations in the choroid plexus and cerebrospinal fluid protein composition. 2D gel electrophoresis in cerebrospinal fluid extracted from the cistern magna before sacrifice of hypertensive and control rats was performed. The results showed different proteomic profiles between SHR and WKY, that ?-1-antitrypsin, apolipoprotein A1, albumin, immunoglobulin G, vitamin D binding protein, haptoglobin and ?-1-macroglobulin were found to be up-regulated in SHR, and apolipoprotein E, transthyretin, ?-2-HS-glycoprotein, transferrin, ?-1?-glycoprotein, kininogen and carbonic anhidrase II were down-regulated in SHR. The conclusion made here is that hypertension in SHR produces important variations in cerebrospinal fluid proteins that could be due to a choroid plexus dysfunction and this fact supports the close connection between hypertension and blood to cerebrospinal fluid barrier disruption. PMID:23401751

  14. Meningitis

    NSDL National Science Digital Library

    Patient Education Institute

    This patient education program discusses meningitis including the causes, symptoms, diagnosis, treatment, complications, infectiousness, and prevention of the disease through vaccination. This resource is a MedlinePlus Interactive Health Tutorial from the National Library of Medicine, designed and developed by the Patient Education Institute. NOTE: This tutorial requires a special Flash plug-in, version 4 or above. If you do not have Flash, you will be prompted to obtain a free download of the software before you start the tutorial. You will also need an Acrobat Reader, available as a free download, in order to view the Reference Summary.

  15. Evaluation of Microbial Bacterial and Fungal Diversity in Cerebrospinal Fluid Shunt Infection

    PubMed Central

    Simon, Tamara D.; Pope, Christopher E.; Browd, Samuel R.; Ojemann, Jeffrey G.; Riva-Cambrin, Jay; Mayer-Hamblett, Nicole; Rosenfeld, Margaret; Zerr, Danielle M.; Hoffman, Lucas

    2014-01-01

    Background Cerebrospinal fluid shunt infection can be recalcitrant. Recurrence is common despite appropriate therapy for the pathogens identified by culture. Improved diagnostic and therapeutic approaches are required, and culture-independent molecular approaches to cerebrospinal fluid shunt infections have not been described. Objectives To identify the bacteria and fungi present in cerebrospinal fluid from children with cerebrospinal fluid shunt infection using a high-throughput sequencing approach, and to compare those results to those from negative controls and conventional culture. Methods This descriptive study included eight children ?18 years old undergoing treatment for culture-identified cerebrospinal fluid shunt infection. After routine aerobic culture of each cerebrospinal fluid sample, deoxyribonucleic acid (DNA) extraction was followed by amplification of the bacterial 16S rRNA gene and the fungal ITS DNA region tag-encoded FLX-Titanium amplicon pyrosequencing and microbial phylogenetic analysis. Results The microbiota analyses for the initial cerebrospinal fluid samples from all eight infections identified a variety of bacteria and fungi, many of which did not grow in conventional culture. Detection by conventional culture did not predict the relative abundance of an organism by pyrosequencing, but in all cases, at least one bacterial taxon was detected by both conventional culture and pyrosequencing. Individual bacterial species fluctuated in relative abundance but remained above the limits of detection during infection treatment. Conclusions Numerous bacterial and fungal organisms were detected in these cerebrospinal fluid shunt infections, even during and after treatment, indicating diverse and recalcitrant shunt microbiota. In evaluating cerebrospinal fluid shunt infection, fungal and anaerobic bacterial cultures should be considered in addition to aerobic bacterial cultures, and culture-independent approaches offer a promising alternative diagnostic approach. More effective treatment of cerebrospinal fluid shunt infections is needed to reduce unacceptably high rates of reinfection, and this work suggests that one effective strategy may be reduction of the diverse microbiota present in infection. PMID:24421877

  16. [Diagnosis and biological monitoring of 6 neurosyphilis cases: value of cerebrospinal fluid analysis].

    PubMed

    Caudie, C; Garel, F; Bancel, J; Lombard, C; Vandenberghe, N

    2003-01-01

    Our objective is to assess the relevance of the different laboratory findings in cerebrospinal fluid (CSF) and serum for the diagnosis and survey of active neurosyphilis. A retrospective study of six hospitalized neurosyphilitic patients at Neurological Hospital of Lyon from 1987 to 2002 was carried out. Six males were found, aged from 29 to 72 years. Neurosyphilis can be group in two categories: early (meningeal and meningovascular neurosyphilis) and late (progressive general paralysis and tabes dorsalis). All were tertiary stage and HIV negative. We performed in CSF, white and red cell count, cytology, total protein, glucose levels, in CSF and serum, albumin, total IgG, IgA, IgM for calculation of albumin quotient and IgG, IgA and IgM index. Serological tests for syphilis in CSF and serum are VDRL and TPHA. To increase the reliability of treponema antibody tests, the ratio of serum-to-CSF content of albumin is used to assess intrathecal production of treponema antibodies, especially the treponema pallidum hemagglutination assay (TPHA index). The CSF changes in neurosyphilis included elevated cell count with lymphocytic-plasmocytic cell reaction, increased protein content, strongly positive IgG index, numerous positive IgG oligoclonal bands, positive blood and CSF serology. Serological tests are difficult to interpret. Examination of CSF played a major role in the diagnosis and treatment of all forms of neurosyphilis. The CSF abnormalities improved with clinical improvement, especially in meningeal and vascular neurosyphilis, but the response in paresis and tabes was slower or nonexistent. Pleocytosis and protein are indicators of inflammatory activity in the central nervous system and are used as a clinical guide in the diagnostic, for treatment and re-treatment. PMID:14671754

  17. Prevalence of human parechovirus and enterovirus in cerebrospinal fluid samples in children in Jinju, Korea

    PubMed Central

    Seo, Ji-Hyun; Yeom, Jung Sook; Youn, Hee-Shang; Han, Tae-Hee

    2015-01-01

    Purpose Human parechovirus (HPeV) and enterovirus (EV) are causative agents of a sepsis-like illness in neonates and of infections of the central nervous system in young children. The objectives of this study were to assess the prevalence of HPeV3 and EV infection in young children with a sepsis-like illness or with meningitis in Jinju, Korea. Methods Cerebrospinal fluid (CSF) samples were collected from 267 patients (age range, 1 day to 5 years) and assessed for HPeV and EV by performing reverse transcription polymerase chain reaction assay. Amplification products of the VP3/VP1 region of HPeV and of the VP1 region of EV were sequenced to identify the virus type. Results HPeV and EV were detected in 3.4% and 7.5% of the total CSF samples assessed, respectively. The age distribution of EV-positive patients (median age, 1.4 months) had a significantly broader range than that of HPeV-positive patients (median age, 7.8 months). The peak seasons for HPeV and EV infection were spring and summer, respectively. The clinical symptoms for HPeV and EV infection were similar, and fever was the most common symptom. Pleocytosis was detected in 22.2% of HPeV-positive patients and 35.5% of EV-positive patients. The VP3/VP1 gene sequence of the nine Korean strains clustered most closely with the Japanese strain (AB759202). Conclusion The data indicate that HPeV infection is predominant in young infants (<6 months) and that meningitis without pleocytosis was caused by both HPeV and EV infection in children.

  18. Cerebrospinal fluid cytology of an endolymphatic sac tumor.

    PubMed

    Bynum, Jennifer P; Bishop, Justin; Ali, Syed Z

    2015-04-01

    Endolymphatic sac tumor (ELST) is a rare neoplasm which is seldom evaluated by cytopathology. We report the clinicopathologic course and cytologic cerebrospinal fluid (CSF) findings in a 58-year-old patient with brainstem lesions who originally presented with vertigo but progressed to having left 7th, 8th, 9th, and 10th cranial nerve palsies, right-sided weakness, and occipital headaches. Cytospin of the CSF revealed large epithelioid cells similar to cells seen in a surgical resection of a brain mass three months previously. Review of the surgical specimen revealed a well-differentiated glandular and papillary neoplasm, most consistent with an endolymphatic sac tumor. Diagn. Cytopathol. 2015;43:339-342. © 2014 Wiley Periodicals, Inc. PMID:25354959

  19. Cerebrospinal Fluid Aquaporin-4 Antibody Levels in Neuromyelitis Optica Attacks

    PubMed Central

    Sato, Douglas Kazutoshi; Callegaro, Dagoberto; de Haidar Jorge, Frederico M; Nakashima, Ichiro; Nishiyama, Shuhei; Takahashi, Toshiyuki; Simm, Renata Faria; Apostolos-Pereira, Samira Luisa; Misu, Tatsuro; Steinman, Lawrence; Aoki, Masashi; Fujihara, Kazuo

    2014-01-01

    To elucidate immunopathogenetic roles of aquaporin-4 antibodies in the cerebrospinal fluid (CSF) of neuromyelitis optica spectrum disorders (NMOSD), we analyzed aquaporin-4 antibody titers, cellular and inflammatory markers in the CSF collected from 11 aquaporin-4 antibody seropositive patients. The CSF aquaporin-4 antibody levels during attacks (but not in sera) closely correlated with pleocytosis, inflammatory cytokines including interleukin-6 that can regulate antibody-producing plasmablasts, and glial fibrillary acidic protein levels in the CSF. The amount of aquaporin-4 antibodies present in the central nervous system may have therapeutic implications, as it is associated with astrocyte injury and inflammatory responses during NMOSD attacks. Ann Neurol 2014;76:305–309 PMID:24977390

  20. Agitation in Dementia: Relation to Core Cerebrospinal Fluid Biomarker Levels

    PubMed Central

    Bloniecki, Victor; Aarsland, Dag; Cummings, Jeffrey; Blennow, Kaj; Freund-Levi, Yvonne

    2014-01-01

    Background The objective of this study was to examine the associations of agitation with the cerebrospinal fluid dementia biomarkers total-tau (T-tau), phosphorylated-tau (P-tau) and A?1-42. Methods One hundred patients (mean age ± SD, 78.6 ± 7.5 years) with dementia and neuropsychiatric symptoms, of whom 67% were female, were included. Agitation was measured using the Cohen-Mansfield Agitation Inventory (CMAI; 46.5 ± 11.8 points). Results Total CMAI correlated with T-tau [rs (31) = 0.36, p = 0.04] and P-tau [rs (31) = 0.35, p = 0.05] in patients with Alzheimer's disease (AD; n = 33) but not in the total dementia population (n = 95). Conclusions Our results suggest that tau-mediated pathology including neurofibrillary tangles and the intensity of the disease process might be associated with agitation in AD. PMID:25298777

  1. The cerebrospinal fluid: regulator of neurogenesis, behavior, and beyond

    PubMed Central

    Zappaterra, Mauro W.; Lehtinen, Maria K.

    2013-01-01

    The cerebrospinal fluid (CSF) has attracted renewed interest as an active signaling milieu that regulates brain development, homeostasis, and disease. Advances in proteomics research have enabled an improved characterization of the CSF from development through adulthood, and key neurogenic signaling pathways that are transmitted via the CSF are now being elucidated. Due to its immediate contact with neural stem cells in the developing and adult brain, the CSF's ability to swiftly distribute signals across vast distances in central nervous system is opening avenues to novel and exciting therapeutic approaches. In this review, we will discuss the development of the choroid plexus-CSF system, and review the current literature on how the CSF actively regulates mammalian brain development, behavior, and responses to traumatic brain injury. PMID:22415326

  2. Parameter estimations for the cerebrospinal fluid infusion test.

    PubMed

    Eisenträger, Almut; Sobey, Ian; Czosnyka, Marek

    2013-06-01

    We consider parameter estimation for a single compartment model of a cerebrospinal fluid (CSF) infusion test using an inverse power law cerebral compliance depending on intracranial pressure (ICP). A least squares optimization is used to solve the inverse problem of estimating model parameter values from ICP observed during an infusion test. The optimization is applied to synthetic test data and to clinical ICP data from a number of infusion tests.We show that in tests that successfully reach a new plateau pressure, the resistance to CSF outflow and elastance can be reliably estimated using an automated least squares process. We find that a single infusion test does not provide enough resolution to distinguish between compliance models. PMID:22345141

  3. Orbital cerebrospinal fluid accumulation after complicated pterional-orbitozygomatic craniotomy.

    PubMed

    Yoon, Michael K; Piluek, Wachirapon Jordan; Ruggiero, Jason P; McDermott, Michael W; McCulley, Timothy J

    2014-12-01

    We describe 2 patients who developed postoperative orbital cerebrospinal fluid (CSF) collection after orbitozygomatic pterional craniotomy. An 18-year-old woman underwent exploratory pterional-orbitozygomatic craniotomy. Five days postoperatively, after removal of a lumbar drain, proptosis and a compressive optic neuropathy developed. Computed tomography demonstrated a CSF collection contiguous with the craniotomy site. Resolution followed percutaneous aspiration and replacement of the lumbar drain. A 57-year-old woman underwent a pterional-orbitozygomatic craniotomy for removal of a left anterior clinoid meningioma, complicated by a large left hemorrhagic stroke requiring decompressive hemicraniectomy. Extracranial CSF collections accumulated in both the orbit and subgaleal spaces. Resolution followed placement of an external ventricular drain. Based on these cases, the mechanism seems to be the combination of iatrogenic formation of a communication with the subarachnoid space and elevated intracranial pressure. Resolution was achieved by normalizing intracranial pressure. PMID:24699141

  4. Embryonic blood-cerebrospinal fluid barrier formation and function

    PubMed Central

    Bueno, David; Parvas, Maryam; Hermelo, Ismaïl; Garcia-Fernàndez, Jordi

    2014-01-01

    During embryonic development and adult life, brain cavities and ventricles are filled with cerebrospinal fluid (CSF). CSF has attracted interest as an active signaling medium that regulates brain development, homeostasis and disease. CSF is a complex protein-rich fluid containing growth factors and signaling molecules that regulate multiple cell functions in the central nervous system (CNS). The composition and substance concentrations of CSF are tightly controlled. In recent years, it has been demonstrated that embryonic CSF (eCSF) has a key function as a fluid pathway for delivering diffusible signals to the developing brain, thus contributing to the proliferation, differentiation and survival of neural progenitor cells, and to the expansion and patterning of the brain. From fetal stages through to adult life, CSF is primarily produced by the choroid plexus. The development and functional activities of the choroid plexus and other blood–brain barrier (BBB) systems in adults and fetuses have been extensively analyzed. However, eCSF production and control of its homeostasis in embryos, from the closure of the anterior neuropore when the brain cavities become physiologically sealed, to the formation of the functional fetal choroid plexus, has not been studied in as much depth and remains open to debate. This review brings together the existing literature, some of which is based on experiments conducted by our research group, concerning the formation and function of a temporary embryonic blood–CSF barrier in the context of the crucial roles played by the molecules in eCSF. PMID:25389383

  5. [Specific serologic reactions in the cerebrospinal fluid in congenital syphilis and therapeutic implications].

    PubMed

    Gendrel, D; Méfane, C; Nardou, M; Moréno, J L; Engohan, E; Toure, R; Moussavou, A; Bénoni, D; Nguemby-Mbina, C

    1990-09-01

    In a study carried out in Gabon, antibodies against the treponema were looked for in the cerebrospinal fluid (CSF) in 13 children with active congenital syphilis (presence of specific IgM antibodies) and in 7 children with positive serologic reactions reflecting transplacental passage of maternal antibodies. Serologic reactions used included the VDRL test, the TPHA test, and the FTA-ABS IgG and IgM tests. Among the 13 children with syphilis, 7 had a positive FTA-ABS IgG test in the CSF; positivity of this test was not correlated with severity of clinical features, CSF protein levels or CSF cytologic findings. The TPHA test was positive in only four children and the VDRL test was consistently negative. These findings are similar to those reported in another group of patients with meningeal involvement proven by the demonstration of IgM in the CSF using recent techniques. Passage of antibodies into the CSF is possible (1 case in this study) but for safety patients with specific IgG in the CSF should be given penicillin in a dosage that provides treponema-killing levels in situ (100,000 U/kg/d). Use of this dosage is recommended whenever sensitive techniques for CSF analysis are not available. PMID:2256636

  6. Cerebrospinal fluid ferritin in HIV infected patients with acute neurological episodes.

    PubMed Central

    Deisenhammer, F; Miller, R F; Brink, N S; Harrison, M J; Thompson, E J

    1997-01-01

    OBJECTIVES: To measure cerebrospinal fluid (CSF) ferritin in HIV infected patients with acute neurological episodes and to correlate the findings with the type and severity of neurological disease. METHODS: CSF ferritin and the ratio of CSF to serum albumin (QAlb) were prospectively measured in 27 consecutive HIV infected patients admitted to a specialist unit for investigation of acute neurological episodes; the results were compared with their clinical diagnoses. RESULTS: Ten patients had HIV associated dementia complex, six had cryptococcal meningitis, two had primary CNS lymphoma and nine had miscellaneous conditions including herpes simplex virus encephalitis, cytomegalovirus encephalitis, cerebral toxoplasmosis and mononeuritis multiplex. Overall, 16 (59%) patients had raised CSF ferritin levels, ranging from 13.0 to 50.2 micrograms/l, (median = 16.1 micrograms/l: normal range = 1.0-12.0 micrograms/l). Thirteen of the 16 also had normal QAlb values, implying an intact CSF-blood barrier, and thus that local synthesis of ferritin had occurred. Elevated ferritin levels were not associated with particular neurological diagnoses. In those with HIV associated dementia complex there was no correlation between CSF ferritin levels and the severity of clinical cognitive deficit or the extent of magnetic resonance imaging abnormalities. CONCLUSIONS: An elevated CSF ferritin level is a non-specific finding in HIV infected patients presenting with acute neurological episodes. PMID:9306897

  7. High cerebrospinal fluid levels of interleukin-10 attained by AAV in dogs.

    PubMed

    Pleticha, J; Malkmus, S A; Heilmann, L F; Veesart, S L; Rezek, R; Xu, Q; Yaksh, T L; Beutler, A S

    2015-02-01

    Intrathecal (IT) gene transfer using adeno-associated virus (AAV) may be clinically promising as a treatment for chronic pain if it can produce sufficiently high levels of a transgene product in the cerebrospinal fluid (CSF). Although this strategy was developed in rodents, no studies investigating CSF levels of an analgesic or antiallodynic protein delivered by IT AAV have been performed in large animals. Interleukin-10 (IL-10) is an antiallodynic cytokine for which target therapeutic levels have been established in rats. The present study tested IT AAV8 encoding either human IL-10 (hIL-10) or enhanced green fluorescent protein (EGFP) in a dog model of IT drug delivery. AAV8/hIL-10 at a dose of 3.5 × 10(12) genome copies induced high hIL-10 levels in the CSF, exceeding the target concentration previously found to be antiallodynic in rodents by >1000-fold. AAV8/EGFP targeted the primary sensory and motor neurons and the meninges. hIL-10, a xenogeneic protein in dogs, induced anti-hIL-10 antibodies detectable in the CSF and serum of dogs. The high hIL-10 levels demonstrate the efficacy of AAV for delivery of secreted transgenes into the IT space of large animals, suggesting a strong case for further development toward clinical testing. PMID:25354684

  8. Sealing of cerebrospinal fluid leakage during conventional transsphenoidal surgery using a fibrin-coated collagen fleece.

    PubMed

    Hong, Chang Ki; Kim, Yong Bae; Hong, Je Beom; Lee, Kyu Sung

    2015-04-01

    The prevention of cerebrospinal fluid (CSF) leakage is a key feature of the transsphenoidal approach (TSA) to the pituitary fossa. Although fibrin-coated collagen fleece (Tachosil, Nycomed, Linz, Austria) is a powerful topical hemostatic agent whose usage is increasing in open neurosurgery, the use of Tachosil in TSA surgery has not yet gained wide clinical acceptance. We retrospectively evaluated whether the lone use of Tachosil without additional packing material or postoperative lumbar drainage was effective to prevent CSF leakage in TSA surgery in 101 patients. Additionally, we compared it to a conventional sellar closure technique in 54 patients. Only two (1.9%) of the patients in the Tachosil application group developed postoperative CSF rhinorrhea. No other postoperative complications occurred, including infection or material detachment. However, in the conventional packing group, five (9.3%) patients developed postoperative CSF rhinorrhea and one (1.9%) developed meningitis during the postoperative period. The mean length of postoperative hospital stay was significantly shorter in the Tachosil treatment group than in the standard closure group. These results may indicate that sellar repair using Tachosil can be effective to prevent CSF leakage after TSA surgery, and obviate the need for an autologous tissue graft or postoperative lumbar drainage. PMID:25630424

  9. Idiopathic cerebrospinal fluid overproduction: case-based review of the pathophysiological mechanism implied in the cerebrospinal fluid production

    PubMed Central

    Trevisi, Gianluca; Frassanito, Paolo; Di Rocco, Concezio

    2014-01-01

    Cerebrospinal fluid (CSF) overproduction results from either CSF infection or choroid plexus hypertrophy or tumor, with only a single idiopathic case described so far. We report a unique case of a male infant with Crouzon syndrome who presented with intracranial hypertension, caused by up to 4-fold increase in CSF daily production. Conditions related to CSF overproduction, namely central nervous system infections and choroid plexus hypertrophy or tumor, were ruled out by repeated magnetic resonance imaging and CSF samples. Medical therapy failed to reduce CSF production and the patient underwent several shunting procedures, cranial expansion, and endoscopic coagulation of the choroid plexus. This article thoroughly reviews pertinent literature on CSF production mechanisms and possible therapeutic implications. PMID:25165051

  10. Cerebrospinal fluid ceramides from patients with multiple sclerosis impair neuronal bioenergetics.

    PubMed

    Vidaurre, Oscar G; Haines, Jeffery D; Katz Sand, Ilana; Adula, Kadidia P; Huynh, Jimmy L; McGraw, Corey A; Zhang, Fan; Varghese, Merina; Sotirchos, Elias; Bhargava, Pavan; Bandaru, Veera Venkata Ratnam; Pasinetti, Giulio; Zhang, Weijia; Inglese, Matilde; Calabresi, Peter A; Wu, Gang; Miller, Aaron E; Haughey, Norman J; Lublin, Fred D; Casaccia, Patrizia

    2014-08-01

    Axonal damage is a prominent cause of disability and yet its pathogenesis is incompletely understood. Using a xenogeneic system, here we define the bioenergetic changes induced in rat neurons by exposure to cerebrospinal fluid samples from patients with multiple sclerosis compared to control subjects. A first discovery cohort of cerebrospinal fluid from 13 patients with multiple sclerosis and 10 control subjects showed that acute exposure to cerebrospinal fluid from patients with multiple sclerosis induced oxidative stress and decreased expression of neuroprotective genes, while increasing expression of genes involved in lipid signalling and in the response to oxidative stress. Protracted exposure of neurons to stress led to neurotoxicity and bioenergetics failure after cerebrospinal fluid exposure and positively correlated with the levels of neurofilament light chain. These findings were validated using a second independent cohort of cerebrospinal fluid samples (eight patients with multiple sclerosis and eight control subjects), collected at a different centre. The toxic effect of cerebrospinal fluid on neurons was not attributable to differences in IgG content, glucose, lactate or glutamate levels or differences in cytokine levels. A lipidomic profiling approach led to the identification of increased levels of ceramide C16:0 and C24:0 in the cerebrospinal fluid from patients with multiple sclerosis. Exposure of cultured neurons to micelles composed of these ceramide species was sufficient to recapitulate the bioenergetic dysfunction and oxidative damage induced by exposure to cerebrospinal fluid from patients with multiple sclerosis. Therefore, our data suggest that C16:0 and C24:0 ceramides are enriched in the cerebrospinal fluid of patients with multiple sclerosis and are sufficient to induce neuronal mitochondrial dysfunction and axonal damage. PMID:24893707

  11. Rickettsial meningitis.

    PubMed

    Salva, Inês; de Sousa, Rita; Gouveia, Catarina

    2014-01-01

    Rickettsial infections are common in southern Europe and the most frequent and lethal type is Mediterranean spotted fever, caused by Rickettsia conorii. The disease is usually characterised by the classical triad of fever, eschar and rash, and is generally a mild disease in children. Complications including neurological involvement are rarely described. We report an unusual case of meningitis in an 18-year-old man, presenting during summer with fever and persistent headache. The cerebrospinal fluid analysis revealed increased cellularity (107 cells/?L), hypoglycorrhachia (50% of glycaemia) and hyperproteinorrhachia (284 mg/dL). Rickettsial infection was confirmed by serology and the patient was treated with doxycycline, with a favourable outcome. The patient's pet squirrel and/or associated vectors might be involved in the transmission of Rickettsia spp. This case underlines the importance of a high clinical suspicion and the benefits of early empirical treatment when facing compatible epidemiological contexts. PMID:24614778

  12. Cytomegalovirus Antibody in Cerebrospinal Fluid of Schizophrenic Patients Detected by Enzyme Immunoassay

    NASA Astrophysics Data System (ADS)

    Fuller Torrey, E.; Yolken, Robert H.; Winfrey, C. Jack

    1982-05-01

    By means of enzyme immunoassay techniques to detect the presence of antibody to cytomegalovirus, the cerebrospinal fluid of 178 patients with schizophrenia, 17 patients with bipolar disorders, and 11 other psychiatric patients was compared with that of 79 neurological patients and 41 normal control subjects. The cerebrospinal fluid of 20 of the schizophrenic patients and 3 of the patients with bipolar disorders showed significant increases in immunoglobulin M antibody to cytomegalovirus; no difference was found in patients on or off psychotropic medications.

  13. Embryonic cerebrospinal fluid in brain development: neural progenitor control

    PubMed Central

    Gato, Angel; Alonso, M. Isabel; Martín, Cristina; Carnicero, Estela; Moro, José Antonio; De la Mano, Aníbal; Fernández, José M. F.; Lamus, Francisco; Desmond, Mary E.

    2014-01-01

    Due to the effort of several research teams across the world, today we have a solid base of knowledge on the liquid contained in the brain cavities, its composition, and biological roles. Although the cerebrospinal fluid (CSF) is among the most relevant parts of the central nervous system from the physiological point of view, it seems that it is not a permanent and stable entity because its composition and biological properties evolve across life. So, we can talk about different CSFs during the vertebrate life span. In this review, we focus on the CSF in an interesting period, early in vertebrate development before the formation of the choroid plexus. This specific entity is called “embryonic CSF.” Based on the structure of the compartment, CSF composition, origin and circulation, and its interaction with neuroepithelial precursor cells (the target cells) we can conclude that embryonic CSF is different from the CSF in later developmental stages and from the adult CSF. This article presents arguments that support the singularity of the embryonic CSF, mainly focusing on its influence on neural precursor behavior during development and in adult life. PMID:25165044

  14. Diagnosis of neurosyphilis by examination of the cerebrospinal fluid.

    PubMed

    Luger, A; Schmidt, B L; Steyrer, K; Schonwald, E

    1981-08-01

    Thirty-six patients with reactive results in the cerebrospinal fluid to the Treponema pallidum haemagglutination assay (CSF-TPHA) were investigated by further serological tests for confirmation of active neurosyphilis. The results of the TPHA and fluorescent treponemal antibody tests were reactive in all CSF samples from patients with acute untreated neurosyphilis and from most patients with late latent syphilis but no signs of involvement of the central nervous system. The demonstration of 19S-IgM antibodies against Treponema pallidum in the CSF was a better indication of activity of the disease than the Venereal Disease Research Laboratory test. Ten of 11 patients with untreated acute neurosyphilis had reactive results in the solid-phase haemadsorption test for CSF-IgM (CSF-IgM-SPHA test). The TPHA index, which relates the CSF-TPHA titre to the albumin quotient and thus excludes errors from disturbed function of the blood-brain barrier, was above 100 in all but one of the patients with acute neurosyphilis but below 100 after treatment. Patients with late latent syphilis and without CNS signs had TPHA indices below 5. Thus a nonreactive CSF-TPHA test result excludes neurosyphilis but reactive CSF-IgM-SPHA results and TPHA indices above 100 strongly indicative active disease. PMID:7023601

  15. Response of cerebrospinal fluid pressure to hyperbaric oxygenation1

    PubMed Central

    Hayakawa, T.; Kanai, N.; Kuroda, R.; Yamada, R.; Mogami, H.

    1971-01-01

    The response of cerebrospinal fluid pressure (CSFP) to hyperbaric oxygenation (OHP) was investigated in 13 patients with acute cerebral damage and in dogs with or without experimentally produced cerebral damage. To elucidate the mechanism of the CSFP response, continuous measurements of carotid blood flow, arterial blood pressure, central venous pressure, and superior sagittal sinus pressure and CSFP were made before, during and after OHP. There was considerable variation in the response of CSFP to OHP in the patients, but three main patterns emerged; type I (nine cases), CSFP decreased at the beginning and rose again at the end of OHP, type II (two cases), CSFP fell with OHP and remained significantly lower than pretreatment level after it, and type III (two cases), CSFP showed little change with OHP. An animal without cerebral damage commonly showed a type I response of CSFP to OHP; the changes of CSFP at the beginning and end of OHP are mainly due to the changes of the cerebral blood flow. There may be two different actions of OHP on cerebral oedema, one decreasing cerebral oedema and another (mainly affecting the normal brain) producing cerebral oedema. Information obtained from the response of CSFP to OHP may be useful in judging the severity and pathophysiological state of cerebral damage. PMID:5122387

  16. The partitioning of cimetidine into canine cerebrospinal fluid.

    PubMed

    Ziemniak, J A; Shank, R G; Schentag, J J

    1984-01-01

    The pharmacokinetics and cerebrospinal fluid (CSF) partitioning of cimetidine were studied in the dog. Four healthy male mongrel dogs were given a 22 mg/kg iv dose of cimetidine. The dogs demonstrated metabolic and pharmacokinetic characteristics similar to human volunteers, as the total body clearance of cimetidine averaged 7.5 ml/min/kg in the dog as compared to 7.7 ml/min/kg in humans. Autopsy tissue concentrations were similar to those measured in humans. There were no statistical differences between dogs and humans in any pharmacokinetic parameters. Cimetidine sulfoxide was the major metabolite in the dog, similar to that in humans. Cimetidine CSF partitioning, as determined by the ratio of cimetidine CSF:serum area under the curve was 0.125 +/- 0.03. Cimetidine appears to enter the CSF by passive diffusion, and is removed by passive diffusion, CSF bulk flow, and possibly by an active transport process. We conclude that the dog is an appropriate animal to investigate cimetidine pharmacokinetics and is a suitable model for examining the CSF uptake of H2-antagonists. PMID:6144488

  17. Endoscopic Management of Cerebrospinal Fluid Rhinorrhea: The Charing Cross Experience

    PubMed Central

    Virk, Jagdeep Singh; Elmiyeh, Behrad; Saleh, Hesham A.

    2013-01-01

    Objective?To describe our experience of cerebrospinal fluid (CSF) rhinorrhea management. Design?Retrospective. Setting?Charing Cross Hospital, London, a tertiary referral center. Participants?Fifty-four patients with CSF rhinorrhea managed from 2003 to 2011. Main outcome measures?Surgical technique; Recurrence. Results?Etiologically, 36 were spontaneous and 18 traumatic. Eight patients with spontaneous and two with traumatic leaks had previous failed repairs in other units. Success rates after first and second surgery were 93% and 100%, respectively. Mean follow-up was 21 months. Four patients, all of spontaneous etiology, had recurrences; three of these underwent successful second repair with three layered technique, and the fourth had complete cessation of the leak after gastric bypass surgery and subsequent weight reduction. Adaptation of anatomic three-layered repair since then averted any further failure in the following 7 years. Mean body mass index was 34.0 kg/m2 in spontaneous and 27.8 kg/m2 in traumatic cases (p?

  18. Cerebrospinal fluid rhinorrhea: An institutional perspective from Pakistan

    PubMed Central

    Tahir, Muhammad Zubair; Khan, Muhammad Babar; Bashir, Muhammad Umair; Akhtar, Shabbir; Bari, Ehsan

    2011-01-01

    Background: The management of cerebrospinal fluid (CSF) rhinorrhea has evolved over the last two decades. We present here a review of our 11-year data on CSF rhinorrhea and its management at a tertiary care hospital in a developing country, with particular reference to the diagnosis, surgical management and outcome of the disease. Methods: The medical charts of all patients with a diagnosis of CSF rhinorrhea over an 11-year period were reviewed. The etiology of CSF rhinorrhea was classified into three categories: spontaneous, iatrogenic and traumatic. All the patients were divided into three categories based on the type of management as conservative, intracranial and transnasal endoscopic groups. Results: A total of 43 patients fulfilled our inclusion criteria and were included in the final analysis. Eleven of the 43 patients were managed conservatively, while 22 underwent intracranial repairs; 10 patients had transnasal endoscopic repairs. The primary success rate for the transnasal approach was 70% compared to 86% for the intracranial repair. Blood loss, special care unit (SCU) stay and total cost were found to be significantly less in the transnasal endoscopic group. Computed tomography (CT) cisternography was found to have the highest sensitivity and specificity. Further, no postoperative complications were found in the transnasal endoscopic group, while five patients from the intracranial group developed various complications. Conclusions: We conclude that the transnasal endoscopic approach has comparable success rates with the intracranial approach and significantly lower morbidity. PMID:22276229

  19. Embryonic cerebrospinal fluid in brain development: neural progenitor control.

    PubMed

    Gato, Angel; Alonso, M Isabel; Martín, Cristina; Carnicero, Estela; Moro, José Antonio; De la Mano, Aníbal; Fernández, José M F; Lamus, Francisco; Desmond, Mary E

    2014-08-28

    Due to the effort of several research teams across the world, today we have a solid base of knowledge on the liquid contained in the brain cavities, its composition, and biological roles. Although the cerebrospinal fluid (CSF) is among the most relevant parts of the central nervous system from the physiological point of view, it seems that it is not a permanent and stable entity because its composition and biological properties evolve across life. So, we can talk about different CSFs during the vertebrate life span. In this review, we focus on the CSF in an interesting period, early in vertebrate development before the formation of the choroid plexus. This specific entity is called "embryonic CSF." Based on the structure of the compartment, CSF composition, origin and circulation, and its interaction with neuroepithelial precursor cells (the target cells) we can conclude that embryonic CSF is different from the CSF in later developmental stages and from the adult CSF. This article presents arguments that support the singularity of the embryonic CSF, mainly focusing on its influence on neural precursor behavior during development and in adult life. PMID:25165044

  20. Human Neurocysticercosis: Comparison of Different Diagnostic Tests Using Cerebrospinal Fluid ?

    PubMed Central

    Michelet, Lorraine; Fleury, Agnès; Sciutto, Edda; Kendjo, Eric; Fragoso, Gladis; Paris, Luc; Bouteille, Bernard

    2011-01-01

    Neurocysticercosis (NC), caused by the larval stage of Taenia solium, is one of the most common parasitic diseases of the central nervous system. The diagnosis of NC is mostly based on costly brain neuroimaging (computed tomography and/or nuclear magnetic resonance), which is rarely accessible in most affected areas. The most sensitive and specific tools for NC diagnosis are imagery techniques. The identification of specific antibodies and antigens is currently used only to support NC diagnosis due to their limited specificity and sensitivity. This study was performed to compare immunodiagnostic assays (antibody detection by enzyme-linked immunosorbent assay [ELISA] and enzyme-linked immunoelectrotransfer blotting [EITB] and HP10 antigen detection by ELISA) with the detection of parasite DNA by PCR amplification of a repetitive element of the parasite genome in the cerebrospinal fluid (CSF) of 121 radiologically and clinically characterized NC patients. Patients were divided into six groups according to the stage of the parasites and their localization. The CSF cellularity of each patient was also recorded. When all patients were considered, PCR exhibited the highest sensitivity (95.9%) and variable specificity (80% or 100%) depending on the controls used. The sensitivities of antibody detection by ELISA and EITB were not significantly different, and ELISA identified HP10 antigen mostly when vesicular cysticerci were located in the subarachnoideal basal cisterns. These results can help in the selection of different individual assays or combinations of assays to be used in NC diagnosis according to different requirements. PMID:21068283

  1. Cerebrospinal fluid and plasma clusterin levels in Parkinson's disease.

    PubMed

    van Dijk, Karin D; Jongbloed, Wesley; Heijst, Johannes A; Teunissen, Charlotte E; Groenewegen, Henk J; Berendse, Henk W; van de Berg, Wilma D J; Veerhuis, Robert

    2013-12-01

    Clusterin is a multifunctional chaperone protein that has repeatedly been linked to Alzheimer's disease (AD) pathogenesis and, more recently, also to Parkinson's disease (PD) by both genetic and proteomic analyses. Although clusterin is detectable in cerebrospinal fluid (CSF) and plasma, studies comparing clusterin levels in PD patients and controls have been scarce and yielded conflicting data. The aim of the present study was to determine whether CSF and/or plasma clusterin levels differ between PD patients and controls and are related to disease severity. We measured CSF and plasma clusterin levels in a group of 52 PD patients and in 50 age-matched neurologically healthy controls and found that clusterin levels in CSF and plasma were not different between the two groups. Furthermore, clusterin levels in CSF and plasma were not associated with disease duration, stage or severity. CSF clusterin levels did, however, correlate with CSF levels of total tau, phospho-tau and amyloid-?-42. We elaborate on the identified correlations between levels of clusterin and AD related proteins and on possible explanations for the discrepant findings in clusterin studies in PD so far. PMID:23932065

  2. Cerebrospinal fluid biomarkers in idiopathic normal pressure hydrocephalus.

    PubMed

    Leinonen, Ville; Menon, Lata G; Carroll, Rona S; Dello Iacono, Donna; Grevet, Jeremy; Jääskeläinen, Juha E; Black, Peter M

    2011-01-01

    The diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is still challenging. Alzheimer's disease (AD), along with vascular dementia, the most important differential diagnosis for iNPH, has several potential cerebrospinal fluid (CSF) biomarkers which might help in the selection of patients for shunt treatment. The aim of this study was to compare a battery of CSF biomarkers including well-known AD-related proteins with CSF from patients with suspected iNPH collected from the external lumbar drainage test (ELD). A total of 35 patients with suspected iNPH patients were evaluated with ELD. CSF was collected in the beginning of the test, and the concentrations of total tau, ptau(181), A?(42), NFL, TNF-?, TGF?1, and VEGF were analysed by ELISA. Twenty-six patients had a positive ELD result-that is, their gait symptoms improved; 9?patients had negative ELD. The levels of all analyzed CSF biomarkers were similar between the groups and none of them predicted the ELD result in these patients. Contrary to expectations lumbar CSF TNF-? concentration was low in iNPH patients. PMID:21660204

  3. Surgical challenge: endoscopic repair of cerebrospinal fluid leak

    PubMed Central

    2012-01-01

    Background Cerebrospinal fluid leaks (CSF) result from an abnormal communication between the subarachnoid space and the extracranial space. Approximately 90% of CSF leak at the anterior skull base manifests as rhinorrhea and can become life-threatening condition. Endoscopic sinus surgery (ESS) has become a common otolaryngologist procedure. The aim of this article is to consider our experience and to evaluate the outcomes in patients who underwent a purely endoscopic repair of CSF leaks of the anterior skull base. Findings Retrospective chart review was performed of all patients surgically treated for CSF leaks presenting to the Section of Nasal and Sinus Disorders at the Service of ENT–Head and Neck Surgery, University Hospital Complex of Santiago de Compostela (CHUS), between 2004 and 2010. A total of 30 patients who underwent repair CSF leak by ESS. The success rate was 93.4% at the first attempt; only two patients (6.6%) required a second surgical procedure, and none of it was necessary to use a craniotomy for closure. Follow-up periods ranged from 4?months to 6?years. Conclusion Identifying the size, site, and etiology of the CSF leak remains the most important factor in the surgical success. It is generally accepted that the ESS have made procedures minimally invasive, and CSF leak is now one of its well-established indications with low morbidity and high success rate, with one restriction for fistulas of the posterior wall of the frontal sinus should be repaired in conjunction with open techniques. PMID:22925201

  4. Vitamin B6 in Plasma and Cerebrospinal Fluid of Children

    PubMed Central

    Albersen, Monique; Bosma, Marjolein; Jans, Judith J. M.; Hofstede, Floris C.; van Hasselt, Peter M.; de Sain-van der Velden, Monique G. M.; Visser, Gepke; Verhoeven-Duif, Nanda M.

    2015-01-01

    Background Over the past years, the essential role of vitamin B6 in brain development and functioning has been recognized and genetic metabolic disorders resulting in functional vitamin B6 deficiency have been identified. However, data on B6 vitamers in children are scarce. Materials and Methods B6 vitamer concentrations in simultaneously sampled plasma and cerebrospinal fluid (CSF) of 70 children with intellectual disability were determined by ultra performance liquid chromatography-tandem mass spectrometry. For ethical reasons, CSF samples could not be obtained from healthy children. The influence of sex, age, epilepsy and treatment with anti-epileptic drugs, were investigated. Results The B6 vitamer composition of plasma (pyridoxal phosphate (PLP) > pyridoxic acid > pyridoxal (PL)) differed from that of CSF (PL > PLP > pyridoxic acid > pyridoxamine). Strong correlations were found for B6 vitamers in and between plasma and CSF. Treatment with anti-epileptic drugs resulted in decreased concentrations of PL and PLP in CSF. Conclusion We provide concentrations of all B6 vitamers in plasma and CSF of children with intellectual disability (±epilepsy), which can be used in the investigation of known and novel disorders associated with vitamin B6 metabolism as well as in monitoring of the biochemical effects of treatment with vitamin B6. PMID:25760040

  5. Reduced cerebrospinal fluid ethanolamine concentration in major depressive disorder

    PubMed Central

    Ogawa, Shintaro; Hattori, Kotaro; Sasayama, Daimei; Yokota, Yuki; Matsumura, Ryo; Matsuo, Junko; Ota, Miho; Hori, Hiroaki; Teraishi, Toshiya; Yoshida, Sumiko; Noda, Takamasa; Ohashi, Yoshiaki; Sato, Hajime; Higuchi, Teruhiko; Motohashi, Nobutaka; Kunugi, Hiroshi

    2015-01-01

    Amino acids play key roles in the function of the central nervous system, and their alterations are implicated in psychiatric disorders. In the search for a biomarker for major depressive disorder (MDD), we used high-performance liquid chromatography to measure amino acids and related molecules in the cerebrospinal fluid (CSF) of 52 patients with MDD (42 depressed and 10 remitted; DSM-IV) and 54 matched controls. Significant differences were found in four amino acid concentrations between the depressed patients and controls. After Bonferroni correction, only ethanolamine (EA) levels remained significantly reduced in depressed patients (nominal P = 0.0000011). A substantial proportion of the depressed patients (40.5%) showed abnormally low CSF EA levels (<12.1??M) (P = 0.000033; OR = 11.6, 95% CI: 3.1–43.2). When patients with low EA and those with high EA levels were compared, the former had higher scores for overall depression severity (P = 0.0033) and ‘Somatic Anxiety’ symptoms (P = 0.00026). In unmedicated subjects, CSF EA levels showed a significant positive correlation with levels of homovanillic acid (P = 0.0030) and 5-hydroxyindoleacetic acid (P = 0.019). To our knowledge, this is the first study showing that patients with MDD have significantly lower CSF EA concentrations compared with control subjects. CSF EA could be a state-dependent biomarker for a subtype of MDD. PMID:25589364

  6. Lateral sphenoid sinus recess cerebrospinal fluid leak: a case series.

    PubMed

    Melo, Nelson Almeida d'Ávila; Borges, Bruno Barros Pinto; Magliarelli Filho, Pedro Augusto; Godoy, Maria Dantas Costa Lima; Pereira, Larissa Vilela; Pinna, Fabio de Rezende; Voegels, Richard Louis

    2014-09-01

    The lateral recess of the sphenoid sinus is one of the most common sites of meningocele and spontaneous cerebrospinal fluid (CSF) leak. Despite the availability of several techniques for closure of skull base defects occurring in this location, recurrence still poses a major challenge. This report reviews the experience of surgical repair of lateral sphenoid sinus recess CSF leak at a tertiary referral center and provides a brief discussion of this rare lesion. Nine surgeries were performed for six cases of spontaneous lateral sphenoid sinus recess CSF leak (two revisions and one repair of a new defect). Two patients presented with intracranial hypertension (ICH) and four with meningocele or meningoencephalocele. The transpterygoid approach was used in two procedures. A multilayer graft was used in seven cases and a nasoseptal flap in two. Three patients received lumbar or ventricular shunts, and one received acetazolamide for ICH management. Two minor complications were recorded, and the overall surgical success rate was 78 %. We conclude that nasoseptal flaps are a valid option for repair of recurrent CSF leaks, particularly in the lateral sphenoid sinus recess. Furthermore, identification and correction of ICH plays an essential role in the success of treatment in this patient population. PMID:24748381

  7. Cryptococcus neoformans meningitis with negative cryptococcal antigen: Evaluation of a new immunochromatographic detection assay.

    PubMed

    Opota, O; Desgraz, B; Kenfak, A; Jaton, K; Cavassini, M; Greub, G; Prod'hom, G; Giulieri, S

    2015-03-01

    Detection of cryptococcal antigen in serum or cerebrospinal fluid allows cryptococcal meningitis diagnosis within few hours with >90% sensitivity. In an HIV-positive patient with Cryptococcus neoformans meningitis, initial antigen detection by immunoagglutination was negative. We thus evaluated a new immunochromatographic detection assay that exhibited a higher sensitivity. PMID:25755893

  8. Vaccine-Induced Waning of Haemophilus influenzae Empyema and Meningitis, Angola

    PubMed Central

    Peltola, Heikki; Bernardino, Luis; Monteiro, Lurdes; Silvestre, Silvia da Conceição; Anjos, Elizabete; Cruzeiro, Manuel Leite; Pitkäranta, Anne; Roine, Irmeli

    2014-01-01

    In Angola during 2003–2012, we detected Haemophilus influenzae in 18% of 2,634 and 26% of 2,996 bacteriologically positive pleural or cerebrospinal fluid samples, respectively, from children. After vaccination launch in 2006, H. influenzae empyema declined by 83% and meningitis by 86%. Severe H. influenzae pneumonia and meningitis are preventable by vaccination. PMID:25340259

  9. Cryptococcus neoformans meningitis with negative cryptococcal antigen: Evaluation of a new immunochromatographic detection assay

    PubMed Central

    Opota, O.; Desgraz, B.; Kenfak, A.; Jaton, K.; Cavassini, M.; Greub, G.; Prod'hom, G.; Giulieri, S.

    2014-01-01

    Detection of cryptococcal antigen in serum or cerebrospinal fluid allows cryptococcal meningitis diagnosis within few hours with >90% sensitivity. In an HIV-positive patient with Cryptococcus neoformans meningitis, initial antigen detection by immunoagglutination was negative. We thus evaluated a new immunochromatographic detection assay that exhibited a higher sensitivity. PMID:25755893

  10. Combination antifungal therapies for HIV-associated cryptococcal meningitis: a randomised trial

    Microsoft Academic Search

    Annemarie E Brouwer; Adul Rajanuwong; Wirongrong Chierakul; George E Griffin; Robert A Larsen; Nicholas J White; Thomas S Harrison

    2004-01-01

    BACKGROUND: It frequently takes more than 2 weeks for drug treatments for cryptococcal meningitis to sterilise cerebrospinal fluid (CSF). In-vitro and animal studies lend support to the use of combinations of amphotericin B, flucytosine, and fluconazole for treatment of cryptococcosis. We compared the fungicidal activity of combinations of these drugs for initial treatment of patients with cryptococcal meningitis. METHODS: 64

  11. Multilevel Intramedullary Spinal Neurocysticercosis With Eosinophilic Meningitis

    PubMed Central

    Torabi, Amir M.; Quiceno, Mary; Mendelsohn, Dianne B.; Powell, Craig M.

    2014-01-01

    Background Cysticercal involvement of the spinal cord is a very rare form of neurocysticercosis. Intramedullary cysts are even less common. Objective To describe a novel presentation of multilevel intramedullary neurocysticercosis with eosinophilic meningitis. Design Case report. Patient A 35-year-old man with a history of cerebral neurocysticercosis who presented with both cauda equina and Brown-Sequard syndromes associated with cerebrospinal fluid findings of eosinophilic meningitis. Results Magnetic resonance imaging confirmed the multilevel intramedullary cord lesions. The patientwas treated medically with dexamethasone and albendazole and had a good recovery. Conclusion Intramedullary neurocysticercosis should be considered as a potentially treatable cause of multilevel spinal lesions with subacute meningitis. PMID:15148157

  12. Cerebrospinal fluid otorrhoea and otorhinorrhoea following closed head injury.

    PubMed

    Henry, R C; Taylor, P H

    1978-09-01

    A discussion of acute traumatic CSF otorrhoea and otorhinorrhoea is presented. The incidence of meningeal infection is reviewed and the management of these cases is outlined with special emphasis on the indications for surgical intervention and the otological procedures available. Two patients who sustained transverse fractures of the petrous temporal bone are described in whom subsequent attacks of meningitis were prevented by a new, simple yet effective operation. PMID:701976

  13. Cerebrospinal Fluid Secretory Ca2+-Dependent Phospholipase A2 Activity: A Biomarker of Blood-Cerebrospinal Fluid Barrier Permeability

    PubMed Central

    Chalbot, Sonia; Zetterberg, Henrik; Blennow, Kaj; Fladby, Tormod; Grundke-Iqbal, Inge; Iqbal, Khalid

    2010-01-01

    The blood-brain barrier, the blood-cerebrospinal fluid barrier (BCB) and other specialized brain barriers are increasingly recognized as a major obstacle to the treatment of most brain disorders. The impairment of these barriers has been implicated in neuropathology of several diseases, such as autism, ischemia, multiple sclerosis and Alzheimer disease. This dual function of the blood-neural barriers points out the importance and need for the development of techniques that can evaluate the nature and level of their integrity. Here we report the discovery of CSF secretory Ca2+-dependent phospholipase A2 (sPLA2) activity as a measure of BCB permeability. Lumbar CSF from BCB-impaired (n=26), multiple sclerosis (n=18) and healthy control (n=32) cases was analyzed using both a newly developed continuous fluorescence assay for CSF sPLA2 activity and CSF/Serum albumin ratio (QAlb), the most common and established method to evaluate BCB permeability. While both measurements showed no significant differences between multiple sclerosis and age-matched normal healthy cases, they were highly correlated. Though the CSF sPLA2 activity and QAlb had over 95 % agreement, the former was found to be more sensitive than the latter in measuring low levels of BCB impairment. PMID:20470866

  14. Cerebrospinal fluid physiology: visualization of cerebrospinal fluid dynamics using the magnetic resonance imaging Time-Spatial Inversion Pulse method.

    PubMed

    Yamada, Shinya

    2014-08-28

    Previously there have been no methods for directly tracing the flow of cerebrospinal fluid (CSF) under physiological conditions, and the circulation of CSF has therefore been studied and visualized by injecting a radioactively labeled tracer or contrast medium visible in x-ray images. The newly developed Time-Spatial Inversion Pulse (Time-SLIP) method makes it possible to directly visualize the flow of CSF using magnetic resonance imaging (MRI), permitting CSF dynamics to be depicted in a certain time frame. The CSF dynamics visualized using Time-SLIP has been found to differ markedly from the classical CSF circulation theory described in medical textbooks. It can be said that research on CSF dynamics has advanced to the next stage with the use of this innovative imaging method. Obtaining a more accurate understanding of normal CSF physiology and pathophysiology should lead to improved diagnostic accuracy, permit the identification of new etiological factors in a variety of diseases, and promote the development of new therapeutic approaches. PMID:25165048

  15. Cerebrospinal fluid physiology: visualization of cerebrospinal fluid dynamics using the magnetic resonance imaging Time-Spatial Inversion Pulse method

    PubMed Central

    Yamada, Shinya

    2014-01-01

    Previously there have been no methods for directly tracing the flow of cerebrospinal fluid (CSF) under physiological conditions, and the circulation of CSF has therefore been studied and visualized by injecting a radioactively labeled tracer or contrast medium visible in x-ray images. The newly developed Time-Spatial Inversion Pulse (Time-SLIP) method makes it possible to directly visualize the flow of CSF using magnetic resonance imaging (MRI), permitting CSF dynamics to be depicted in a certain time frame. The CSF dynamics visualized using Time-SLIP has been found to differ markedly from the classical CSF circulation theory described in medical textbooks. It can be said that research on CSF dynamics has advanced to the next stage with the use of this innovative imaging method. Obtaining a more accurate understanding of normal CSF physiology and pathophysiology should lead to improved diagnostic accuracy, permit the identification of new etiological factors in a variety of diseases, and promote the development of new therapeutic approaches. PMID:25165048

  16. Independent information from cerebrospinal fluid amyloid-? and florbetapir imaging in Alzheimer's disease.

    PubMed

    Mattsson, Niklas; Insel, Philip S; Donohue, Michael; Landau, Susan; Jagust, William J; Shaw, Leslie M; Trojanowski, John Q; Zetterberg, Henrik; Blennow, Kaj; Weiner, Michael W

    2015-03-01

    Reduced cerebrospinal fluid amyloid-?42 and increased retention of florbetapir positron emission tomography are biomarkers reflecting cortical amyloid load in Alzheimer's disease. However, these measurements do not always agree and may represent partly different aspects of the underlying Alzheimer's disease pathology. The goal of this study was therefore to test if cerebrospinal fluid and positron emission tomography amyloid-? biomarkers are independently related to other Alzheimer's disease markers, and to examine individuals who are discordantly classified by these two biomarker modalities. Cerebrospinal fluid and positron emission tomography amyloid-? were measured at baseline in 769 persons [161 healthy controls, 68 subjective memory complaints, 419 mild cognitive impairment and 121 Alzheimer's disease dementia, mean age 72 years (standard deviation 7 years), 47% females] and used to predict diagnosis, APOE ?4 carriage status, cerebral blood flow, cerebrospinal fluid total-tau and phosphorylated-tau levels (cross-sectionally); and hippocampal volume, fluorodeoxyglucose positron emission tomography results and Alzheimer's Disease Assessment Scale-cognitive subscale scores (longitudinally). Cerebrospinal fluid and positron emission tomography amyloid-? were highly correlated, but adjusting one of these predictors for the other revealed that they both provided partially independent information when predicting diagnosis, APOE ?4, hippocampal volume, metabolism, cognition, total-tau and phosphorylated-tau (the 95% confidence intervals of the adjusted effects did not include zero). Cerebrospinal fluid amyloid-? was more strongly related to APOE ?4 whereas positron emission tomography amyloid-? was more strongly related to tau levels (P < 0.05). Discordance (mainly isolated cerebrospinal fluid amyloid-? positivity) differed by diagnostic group (P < 0.001) and was seen in 21% of cognitively healthy people but only 6% in dementia patients. The finding that cerebrospinal fluid and positron emission tomography amyloid-? provide partially independent information about a wide range of Alzheimer's measures supports the theory that these modalities represent partly different aspects of Alzheimer's pathology. The fact that mismatch, with positive cerebrospinal fluid amyloid-? but normal positron emission tomography amyloid-?, is relatively common in cognitively healthy people may be considered when using these biomarkers to identify early stage Alzheimer's disease. Reduced cerebrospinal fluid amyloid-? may be more strongly related to early stage Alzheimer's disease, whereas increased positron emission tomography amyloid-? may be more strongly related to disease progression. PMID:25541191

  17. Interleukin-6 and interleukin-10 in cerebrospinal fluid after severe traumatic brain injury in children.

    PubMed

    Bell, M J; Kochanek, P M; Doughty, L A; Carcillo, J A; Adelson, P D; Clark, R S; Wisniewski, S R; Whalen, M J; DeKosky, S T

    1997-07-01

    Cytokines may play an important role in the pathophysiology of traumatic brain injury (TBI) in children. Interleukin-6 (IL-6) is a proinflammatory cyotkine that plays a role in regenerative processes within the central nervous system (CNS), whereas interleukin-10 (IL-10) is an antiinflammatory cytokine. Both have been measured in serum and cerebrospinal fluid (CSF) as an index of the degree of inflammation in diseases, including sepsis and meningitis. We hypothesized that both IL-6 and IL-10 would be increased in the CSF of children after severe TBI. Fifteen children who sustained severe TBI (Glascow Coma Score [GCS] < or = 7) were studied. Standard neurointensive care was provided. Ventricular CSF collected the first 3 days after TBI was analyzed for IL-6 and IL-10 concentrations by ELISA. Controls were 20 children who were evaluated for meningitis with diagnostic lumbar puncture subsequently found to have no CSF pleocytosis and negative cultures. IL-6 was increased in children after TBI versus controls on all days studied (day 1, 3158.2 +/- 621.8 pg/ml; day 2, 1111.6 +/- 337.0 pg/ml; day 3, 826.7 +/- 193.5 pg/ml vs. 20.6 +/- 5.8 pg/ml, p < 0.0001, Mann-Whitney Rank Sum). IL-10 was increased in children after TBI vs controls on all days studied (day 1, 47.2 +/- 12.9 pg/ml; day 2, 21.0 +/- 6.7 pg/ml; day 3, 15.5 +/- 5.9 pg/ml vs. 8.9 +/- 7.5 pg/ml, p < 0.01). Increased IL-10 concentrations were independently associated with age < 4 years and mortality (p = 0.004 and 0.04, respectively, multivariate linear model). This study demonstrates that IL-6 is increased after TBI in children to levels similar to those reported in adults and is the first to show that IL-10 is increased in CSF of humans after TBI. These data suggest that there may be an age-dependent production of IL-10 after TBI in children. PMID:9257663

  18. Cerebrospinal Fluid Biomarker Candidates Associated with Human WNV Neuroinvasive Disease

    PubMed Central

    Fraisier, Christophe; Papa, Anna; Granjeaud, Samuel; Hintzen, Rogier; Martina, Byron; Camoin, Luc; Almeras, Lionel

    2014-01-01

    During the last decade, the epidemiology of WNV in humans has changed in the southern regions of Europe, with high incidence of West Nile fever (WNF) cases, but also of West Nile neuroinvasive disease (WNND). The lack of human vaccine or specific treatment against WNV infection imparts a pressing need to characterize indicators associated with neurological involvement. By its intimacy with central nervous system (CNS) structures, modifications in the cerebrospinal fluid (CSF) composition could accurately reflect CNS pathological process. Until now, few studies investigated the association between imbalance of CSF elements and severity of WNV infection. The aim of the present study was to apply the iTRAQ technology in order to identify the CSF proteins whose abundances are modified in patients with WNND. Forty-seven proteins were found modified in the CSF of WNND patients as compared to control groups, and most of them are reported for the first time in the context of WNND. On the basis of their known biological functions, several of these proteins were associated with inflammatory response. Among them, Defensin-1 alpha (DEFA1), a protein reported with anti-viral effects, presented the highest increasing fold-change (FC>12). The augmentation of DEFA1 abundance in patients with WNND was confirmed at the CSF, but also in serum, compared to the control individual groups. Furthermore, the DEFA1 serum level was significantly elevated in WNND patients compared to subjects diagnosed for WNF. The present study provided the first insight into the potential CSF biomarkers associated with WNV neuroinvasion. Further investigation in larger cohorts with kinetic sampling could determine the usefulness of measuring DEFA1 as diagnostic or prognostic biomarker of detrimental WNND evolution. PMID:24695528

  19. Cerebrospinal fluid PKR level predicts cognitive decline in Alzheimer's disease.

    PubMed

    Dumurgier, Julien; Mouton-Liger, Francois; Lapalus, Pauline; Prevot, Magali; Laplanche, Jean-Louis; Hugon, Jacques; Paquet, Claire

    2013-01-01

    The cerebrospinal fluid (CSF) levels of the proapoptotic kinase R (PKR) and its phosphorylated PKR (pPKR) are increased in Alzheimer's disease (AD), but whether CSF PKR concentrations are associated with cognitive decline in AD patients remain unknown. In this study, 41 consecutive patients with AD and 11 patients with amnestic mild cognitive impairment (aMCI) from our Memory Clinic were included. A lumbar puncture was performed during the following month of the clinical diagnosis and Mini-Mental State Examination (MMSE) evaluations were repeated every 6 months during a mean follow-up of 2 years. In AD patients, linear mixed models adjusted for age and sex were used to assess the cross-sectional and longitudinal associations between MMSE scores and baseline CSF levels of A? peptide (A? 1-42), Tau, phosphorylated Tau (p-Tau 181), PKR and pPKR. The mean (SD) MMSE at baseline was 20.5 (6.1) and MMSE scores declined over the follow-up (-0.12 point/month, standard error [SE]?=?0.03). A lower MMSE at baseline was associated with lower levels of CSF A? 1-42 and p-Tau 181/Tau ratio. pPKR level was associated with longitudinal MMSE changes over the follow-up, higher pPKR levels being related with an exacerbated cognitive deterioration. Other CSF biomarkers were not associated with MMSE changes over time. In aMCI patients, mean CSF biomarker levels were not different in patients who converted to AD from those who did not convert.These results suggest that at the time of AD diagnosis, a higher level of CSF pPKR can predict a faster rate of cognitive decline. PMID:23320095

  20. [Recurrent episodic unilateral mydriasis with pleocytosis in the cerebrospinal fluid--a case report].

    PubMed

    Takeda, K; Sakuta, M; Takano, T

    1989-09-01

    A 24-year-old female was admitted to our hospital on Aug. 20 in 1986 because of blurred vision and right pupillary dilatation. She had sometimes noticed headache later than 1976, and blurred vision without headache several times a year later than 1983. She had been told her right pupil dilated when she had complained of blurred vision. Neurological examination revealed abnormal findings as follows; diminished sense of smell in the right side, anisocoria (R 8 mm, L 5 mm), bilateral hippus, hypesthesioalgesia in her right face, left trunk and left arm. The pupils were round and contracted promptly to light. Accommodation reflex and ciliospinal reflexes were normal. Neither blepharoptosis nor external ocular muscle paresis were observed. Deep tendon reflexes were normal. Planter responses were flexor. There was no meningeal irritative sign. No abnormal findings were obtained in blood and urine, chest X-p, brain enhanced CT scan, EEG, and cerebral angiography except for slight degree of anemia. Serum TPHA was negative. However, the cell count of cerebrospinal fluid (CSF) was 18/mm3 (Ly 100%) and decreased to 9/mm3 (Ly 100%) in nine days. Protein content and glucose level of CSF were normal. Pupils were not constricted by 0.125% pilocarpine instillation. Loss of smell and sensory disturbance disappeared within three days and her pupils became isocoric by five days after admission. The patients of episodic unilateral mydriasis without apparent cause had relatively same clinical features as "unilateral springing pupil" proposed by Hallett et al. (1970). Except for mydriasis, they had no abnormal findings of neurological and laboratory examinations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2598548

  1. A case of recurrent benign lymphocytic (Mollaret's) meningitis and review of the literature.

    PubMed

    Poulikakos, P J; Sergi, E E; Margaritis, A S; Kioumourtzis, A G; Kanellopoulos, G D; Mallios, P K; Dimitrakis, D J; Poulikakos, D J; Aspiotis, A A; Deliousis, A D; Flevaris, C P; Zacharof, A K

    2010-12-01

    Mollaret's meningitis is a rare form of benign recurrent aseptic meningitis first described in 1944. We report a case of Mollaret's meningitis due to Herpes Simplex Virus type 2 (HSV2), diagnosed with Polymerase Chain Reaction (PCR) implementation in the Cerebrospinal fluid (CSF) of the patient and treated successfully with acyclovir. To our knowledge, this is the first case of Mollaret's meningitis reported in Greece. We reviewed the literature since PCR has become widely available. Herpes Simplex Virus type 2 has been the most commonly identified causative agent of Mollaret's meningitis. PMID:21126724

  2. Three Dimensional Modeling of the Cerebrospinal Fluid Dynamics and Brain Interactions in the Aqueduct of Sylvius

    Microsoft Academic Search

    LoÏc Fin; Reinhard Grebe

    2003-01-01

    A computational fluid dynamics (CFD) method is presented to investigate the flow of cerebro-spinal fluid (CSF) in the cerebral aqueduct. In addition to former approaches exhibiting a rigid geometry, we propose a model which includes a deformable membrane as the wall of this flow channel. An anatomical shape of the aqueduct was computed from magnetic resonance images (MRI) and the

  3. [Recurrent aseptic meningitis in periodic disease or Mollaret's meningitis?].

    PubMed

    Collard, M; Sellal, F; Hirsch, E; Mutschler, V; Marescaux, C

    1991-01-01

    A 33 year-old Sephardic Jewish man with familial mediterranean fever (FMF), presented during a 7 year period, 6 episodes of aseptic meningitis, improving within less than 24 h after spinal tap. Cerebrospinal fluid analysis showed a mixed leucocytic pleocytosis ranging from 100 to 1,000 cell/mm3. Spinal fluid cultures for bacteria, viruses and viral antibodies were always negative. Our case supports other reports showing that recurrent aseptic meningitis, although rare, may occur in FMF. It usually responds to treatment with colchicine, like other manifestations of the disease. FMF meningitis has been compared to Mollaret's meningitis whose cause is undetermined. However, Mollaret's meningitis, unlike FMF, is sporadic and ubiquitous, is not transmitted genetically and affects men and women equally. Moreover, in Mollaret's meningitis transient neurological abnormalities, such as signs of encephalitis have often been reported: polyserositis or associated amylosis are absent, there is no biological inflammatory syndrome, and in 65% of the patients the CSF contains specific large mononuclear-derived cells called endothelial cells. Such abnormalities have not been described in FMF. PMID:1853039

  4. Identification and proteomic profiling of exosomes in human cerebrospinal fluid

    PubMed Central

    2012-01-01

    Background Exosomes are released from multiple cell types, contain protein and RNA species, and have been exploited as a novel reservoir for disease biomarker discovery. They can transfer information between cells and may cause pathology, for example, a role for exosomes has been proposed in the pathophysiology of Alzheimer's disease. Although studied in several biofluids, exosomes have not been extensively studied in the cerebrospinal fluid (CSF) from humans. The objective of this study was to determine: 1) whether human CSF contains exosomes and 2) the variability in exosomal protein content across individuals. Methods CSF was collected from 5 study participants undergoing thoraco-abdominal aortic aneurysm repair (around 200 - 500 ml per participant) and low-density membrane vesicles were concentrated by ultracentrifugation. The presence of exosomes was determined by western blot for marker proteins, isopycnic centrifugation on a sucrose step gradient and transmission electron microscopy with immuno-labelling. Whole protein profiling was performed using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR). Results Flotillin 1 and tumor susceptibility gene 101 (TSG101), two exosomal marker proteins, were identified in the ultracentrifugation pellet using western blot. These markers localized to a density consistent with exosomes following isopycnic centrifugation. Transmission electron microscopy visualized structures consistent with exosomes in size and appearance that labelled positive for flotillin 1. Therefore, the pellet that resulted from ultracentrifugation of human CSF contained exosomes. FT-ICR profiling of this pellet was performed and 84-161 ions were detected per study participant. Around one third of these ions were only present in a single study participant and one third were detected in all five. With regard to ion quantity, the median coefficient of variation was 81% for ions detected in two or more samples. Conclusions Exosomes were identified in human CSF and their proteome is a potential new reservoir for biomarker discovery in neurological disorders such as Alzheimer's disease. However, techniques used to concentrate exosomes from CSF need refinement to reduce variability. In this study we used relatively large starting volumes of human CSF, future studies will focus on exosome isolation from smaller 'real life' clinical samples; a key challenge in the development of exosomes as translational tools. PMID:22221959

  5. Lactobacillus rhamnosus Meningitis following Recurrent Episodes of Bacteremia in a Child Undergoing Allogeneic Hematopoietic Stem Cell Transplantation?

    PubMed Central

    Robin, Frédéric; Paillard, Catherine; Marchandin, Hélène; Demeocq, François; Bonnet, Richard; Hennequin, Claire

    2010-01-01

    We report a case of meningitis due to Lactobacillus rhamnosus in a child undergoing allogeneic hematopoietic stem cell transplantation for acute leukemia. Four episodes of bacteremia involving strains with pulsotypes identical to that of the cerebrospinal fluid isolate preceded meningitis. After several courses of clindamycin, no relapse occurred during the patient follow-up. PMID:20844225

  6. Successful large-volume cerebrospinal fluid aspiration for an accidental overdose of intrathecal cytarabine.

    PubMed

    Makar, Gerges; Al-Zubaidi, Muhanad; Amar, Surabhi; Feiz-Erfan, Iman; Mehta, Divyesh

    2013-06-01

    Intrathecal therapy with cytarabine is widely used in the treatment of acute lymphocytic leukemia. We report the first case of accidental intrathecal cytarabine overdose in an adult patient. Overdose of intrathecal chemotherapy has been reported to cause severe neurological damage including seizures, coma and death. Methotrexate levels can help guide intrathecal dosing of methotrexate, but no such test is commercially available for cytarabine. There are no standardized treatment recommendations for the management of this medical emergency. Intrathecal methotrexate overdose has been variously treated with cerebrospinal fluid drainage or exchange. Ventriculo-lumbar perfusion, steroids and leucovorin have also been used. It seems crucial to quickly remove as much drug as possible from the cerebrospinal fluid. Our patient was successfully treated with large-volume cerebrospinal fluid aspiration through an Ommaya reservoir. She did not suffer any significant immediate or late complications at 4 months of follow-up. PMID:23463468

  7. Neonatal meningitis in Harare, Zimbabwe: a 2-year review.

    PubMed

    Nathoo, K J; Pazvakavamba, I; Chidede, O S; Chirisa, C

    1991-01-01

    A 2-year review of neonatal meningitis was undertaken at a referral hospital in Zimbabwe to determine the pattern of bacterial isolates from the cerebrospinal fluid, the clinical presentation and the immediate outcome. During the study period, 94 cases were identified and the overall mortality was 41%. Group B Streptococcus was the predominant organism isolated (61%) and was associated with 42% mortality. Low-birthweight babies and babies with Gram-negative meningitis had mortality rates of 71 and 62%, respectively. PMID:1714689

  8. Childhood meningitis in the conjugate vaccine era: a prospective cohort study.

    PubMed

    Sadarangani, Manish; Willis, Louise; Kadambari, Seilesh; Gormley, Stuart; Young, Zoe; Beckley, Rebecca; Gantlett, Katherine; Orf, Katharine; Blakey, Sarah; Martin, Natalie G; Kelly, Dominic F; Heath, Paul T; Nadel, Simon; Pollard, Andrew J

    2015-03-01

    Bacterial conjugate vaccines have dramatically changed the epidemiology of childhood meningitis; viral causes are increasingly predominant, but the current UK epidemiology is unknown. This prospective study recruited children under 16?years of age admitted to 3 UK hospitals with suspected meningitis. 70/388 children had meningitis-13 bacterial, 26 viral and 29 with no pathogen identified. Group B Streptococcus was the most common bacterial pathogen. Infants under 3?months of age with bacterial meningitis were more likely to have a reduced Glasgow Coma Score and respiratory distress than those with viral meningitis or other infections. There were no discriminatory clinical features in older children. Cerebrospinal fluid (CSF) white blood cell count and plasma C-reactive protein at all ages, and CSF protein in infants <3?months of age, distinguished between bacterial meningitis and viral meningitis or other infections. Improved diagnosis of non-bacterial meningitis is urgently needed to reduce antibiotic use and hospital stay. PMID:25256088

  9. [Hemophilus aphrophilus meningitis: report of one case].

    PubMed

    Wang, K F; Wu, C M; Wu, L J; Tsang, S C; Chen, H M; Hong, Y C

    1993-01-01

    Hemophilus aphrophilus, a gram negative, capnophilic slow growing bacillus, is a rarely recognized pathogen in meningitis and is most frequently seen in patients with either endocarditis or brain abscess. This article reported one case with Hemophilus aphrophilus meningitis. A 10-year-old boy presented at the emergency room with chief complaint of fever for 2 days and sudden onset of loss of consciousness. Hemophilus aphrophilus was isolated from the blood and cerebrospinal fluid. Aqueous penicillin and chloramphenicol were given for three weeks. The patient discharged without any sequelae. Three months later, fever and consciousness disturbance were noted again. No pathogen was isolated from the cerebrospinal fluid and blood culture this time, but CSF finding was consistent with bacterial meningitis. Aqueous penicillin and chloramphenicol were readministered for 30 days. The patient recovered smoothly. Because the patient had no history of CSF rhinorrhea or hypogammaglobulinemia, recurrence of the bacterial meningitis could be due to incomplete treatment during the first admission. Brain computed tomography (CT) done during the two admissions showed focal cortical enhancement in the fronto-temporo-parietal region. This is presumed to indicate infarction over these regions. The findings of brain CT are in accordance with the development of hemiplegia in the patient. It is still unknown, however, whether Hemophilus aphrophilus meningitis also causes a higher incidence of brain infarction, which was frequently noted in patients with Hemophilus influenzae meningitis. PMID:8237362

  10. Incidence of Cerebrospinal Fluid Leak after Microsurgical Removal of Vestibular Schwannomas

    Microsoft Academic Search

    A. Bani; J. M. Gilsbach

    2002-01-01

    Summary.  \\u000a ?Objectives: Cerebrospinal fluid (CSF) leak still remains an unresolved problem after microsurgical removal of vestibular schwannomas\\u000a (VS).\\u000a \\u000a \\u000a \\u000a ?Methods: 14 (6%) Cases of cerebrospinal fluid rhinorrhea and 3 cases with subcutaneous retro-auricular CSF collection, occurring in\\u000a a series of 224 patients operated on by the senior author (JMG) on VS between 1989–2000 via the suboccipital retrosigmoidal\\u000a approach were studied retrospectively.

  11. Steroid Hormones and Steroid Hormone Binding Globulins in Cerebrospinal Fluid Studied in Individuals with Intact and with Disturbed Blood-Cerebrospinal Fluid Barrier

    Microsoft Academic Search

    Siegfried Schwarz; Peter Pohl

    1992-01-01

    We measured in simultaneously withdrawn cerebrospinal fluid (CSF) and serum samples from 56 endocrinologically grossly normal patients the concentrations of several lipophilic unconjugated steroids [i.e. dehydroepiandrosterone (DHEA), androstenedione, cortisol, progesterone, testosterone] and their hydrophilic counterparts, i.e. DHEA-sulfate, or hydrophilic binding proteins, i.e. albumin, sex hormone-binding globulin (SHBG) and corticosterone-binding globulin (CBG). CSF levels of total (i.e. free plus protein-bound) DHEA,

  12. Simultaneous detection of herpes simplex virus 1 and 2 in the cerebrospinal fluid of a patient with seizures and encephalitis.

    PubMed

    Anderson, Neil W; Sistrunk, William; Binnicker, Matthew J

    2015-01-01

    We report a case of a 62-year-old female with seizures and encephalitis. Molecular testing of the patient's cerebrospinal fluid was positive for both herpes simplex virus 1 and 2 (HSV-1 and HSV-2). To our knowledge, this is the first report of simultaneous detection of HSV-1 and HSV-2 in cerebrospinal fluid. PMID:25355765

  13. Selenium speciation in paired serum and cerebrospinal fluid samples.

    PubMed

    Solovyev, Nikolay; Berthele, Achim; Michalke, Bernhard

    2013-02-01

    Se speciation was performed in 24 individual paired serum and cerebrospinal fluid (CSF) samples from neurologically healthy persons. Strong anion exchange (SAX) separation, coupled to inductively coupled plasma-dynamic reaction cell-mass spectrometry (ICP-DRC-MS), was employed. Species identification was done by standard matched retention time, standard addition and by size exclusion chromatography followed from SAX (2-D SEC-SAX-ICP-DRC-MS) and by SAX followed from CE-ICP-DRC-MS (2-D SAX-CE-ICP-DRC-MS). Limit of detection (LoD, 3×standard deviation (SD) of noise) was in the range of 0.026-0.031 ?g/L for all investigated species and thus was set uniformly to 0.032 ?g/L. Quality control for total Se determination was performed by analysing control materials "human serum" and "urine", where determined values met target values. Several Se species were found in both sample types having following median values (sequence: serum/CSF, each in ?g Se/L): total Se, 58.39/0.86; selenoprotein P (SePP), 5.19/0.47; Se-methionine (SeM), 0.23/?65 ?g/L; however, SePP(-CSF) appeared independent of SePP(-serum). For Se-HSA(-serum) versus (vs.) Se-HSA(-CSF), a weak linear relationship was found (r(2)=0.1722). On the contrary, for anti-oxidative Se-enzymes, higher r (2) values were calculated: GPx(-serum) vs. GPx(-CSF), r(2)=0.3837; TrxR(-serum) vs. TrxR(-CSF), r(2)=0.6293. Q(-Se-species) values (= ratios of CSF(-Se-species)/serum(-Se-species)) were compared with the Q (-Alb) value (HSA(-CSF)/HSA(-serum)=clinical index of NB integrity) for deeper information about NB passage of Se species. The Q (-Se-HSA) value (3.8×10(-3)) was in accordance to the molecular mass dependent restriction at NB (Q(-Alb) at 5.25×10(-3)). Increased Q values were seen for TrxR (21.3×10(-3)) and GPx (8.3×10(-3)) which are not (completely) explained by molecular size. For these two anti-oxidative Se-enzymes (GPx, TrxR), we hypothesize that there might be either a facilitated diffusion across NB or they might be additionally synthesized in the brain. PMID:22868477

  14. Letter to the editor: Identification of Sarcocystis capracanis in cerebrospinal fluid from sheep with neurological disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A recent report (Formisano et al., 2013) identified clinical sacrocystosis in 2 adult sheep. The diagnosis relied primarily on characterization of DNA extracted from cerebrospinal fluid (CSF) and paraffin-embedded heart tissue. Parasites identified as merozoites were identified in CSF smears stained...

  15. ?-Trace protein in human cerebrospinal fluid: a diagnostic marker for N-glycosylation defects in brain

    Microsoft Academic Search

    Stephanie Grünewald; Karin Huyben; Jan G. N de Jong; Jan A. M Smeitink; Estella Rubio; Godfried H. J Boers; Harald S Conradt; Udo Wendel; Ron A Wevers

    1999-01-01

    As carbohydrate-deficient glycoprotein syndromes (CDGS) are multisystemic disorders with impaired central nervous function in nearly all cases, we tested isoforms of ?-trace protein (?TP), a ‘brain-type’ glycosylated protein in cerebrospinal fluid (CSF) of nine patients with the characteristic CDGS type I pattern of serum transferrin. Whereas the serum transferrin pattern did not discriminate between the various subtypes of CDGS type

  16. Elevated levels of tau-protein in cerebrospinal fluid of patients with Creutzfeldt–Jakob disease

    Microsoft Academic Search

    Markus Otto; Jens Wiltfang; Hayrettin Tumani; Inga Zerr; Maria Lantsch; Johannes Kornhuber; Thomas Weber; Hans A Kretzschmar; Sigrid Poser

    1997-01-01

    Creutzfeldt–Jakob disease (CJD) is a rare, fatal, neurodegenerative disease caused by a transmissible agent designated as proteinaceous infectious agent (prion). Searching for biochemical markers of CJD, we analysed cerebrospinal fluid (CSF) samples of 53 patients for tau-protein using an enzyme linked immunoassay (ELISA). In a group of 21 patients with definite CJD seen in the German case control study for

  17. Dynamics of lateral ventricle and cerebrospinal fluid in normal and hydrocephalic brains

    Microsoft Academic Search

    David C. Zhu; Michalis Xenos; Andreas A. Linninger; Richard D. Penn

    2006-01-01

    Purpose: To develop quantitative MRI techniques to mea- sure, model, and visualize cerebrospinal fluid (CSF) hydro- dynamics in normal subjects and hydrocephalic patients. Materials and Methods: Velocity information was obtained using time-resolved (CINE) phase-contrast imaging of dif- ferent brain regions. A technique was developed to measure the change of lateral ventricle (LV) size. The temporal rela- tionships between the LV

  18. Baseline Neuropsychological Profile and Cognitive Response to Cerebrospinal Fluid Shunting for Idiopathic Normal Pressure Hydrocephalus

    Microsoft Academic Search

    George Thomas; Matthew J. McGirt; Graeme Woodworth; Jennifer Heidler; Daniele Rigamonti; Argye E. Hillis; Michael A. Williams

    2005-01-01

    Objective: To evaluate neurocognitive changes and predict neurocognitive outcome after ventriculoperitoneal shunting for idiopathic normal pressure hydrocephalus (INPH). Background: Reports of neurocognitive response to shunting have been variable and studies that predict cognitive outcomes after shunting are limited. We reviewed our experience with cognitive outcomes for INPH patients who were selected for shunting based on abnormal cerebrospinal fluid (CSF) pressure

  19. Cerebrospinal fluid ?-glucocerebrosidase activity is reduced in Dementia with Lewy Bodies

    Microsoft Academic Search

    L. Parnetti; C. Balducci; L. Pierguidi; C. De Carlo; M. Peducci; C. D'Amore; C. Padiglioni; S. Mastrocola; E. Persichetti; S. Paciotti; G. Bellomo; N. Tambasco; A. Rossi; T. Beccari; P. Calabresi

    2009-01-01

    The autophagy–lysosomal degradation pathway plays a role in the onset and progression of neurodegenerative diseases. Clinical and genetic studies indicate that mutations of ?-glucocerebrosidase represent genetic risk factors for synucleinopathies, including Parkinson's Disease (PD) and Dementia with Lewy Bodies (DLB). We recently found a decreased activity of lysosomal hydrolases, namely ?-glucocerebrosidase, in cerebrospinal fluid of PD patients. We have thus

  20. Cerebrospinal fluid flow and production in patients with normal pressure hydrocephalus studied by MRI

    Microsoft Academic Search

    P. Gideon; F. Ståhlberg; C. Thomsen; F. Gjerris; P. S. Sørensen; O. Henriksen

    1994-01-01

    An interleaved velocity-sensitised fast low-angle shot pulse sequence was used to study cerebrospinal fluid (CSF) flow in the cerebral aqueduct, and supratentorial CSF production in 9 patients with normal pressure hydrocephalus (NPH) and 9 healthy volunteers. The peak aqueduct CSF flow, both caudal and rostral, was significantly increased in patients with NPH. No significant difference in the supratentorial CSF production

  1. Normal pressure hydrocephalus: Correlation between CT and measurements of cerebrospinal fluid dynamics

    Microsoft Academic Search

    M. Kosteljanetz; H. M. Ingstrup

    1985-01-01

    Summary Twenty-nine patients consecutively admitted for consideration of CSF diversion surgery for suspected communicating (“normal pressure”) hydrocephalus underwent cranial computerized tomography (CT) and study of cerebrospinal fluid (CSF) absorption, the latter determined as resistance to outflow of CSF (Ro). From the CT the size of the ventricular system was determined by various linear measurements and ratios and the presence of

  2. Volume Assessment of the Cerebrospinal Fluid Spaces for Computer Aided Diagnosis

    E-print Network

    Paris-Sud XI, Université de

    Volume Assessment of the Cerebrospinal Fluid Spaces for Computer Aided Diagnosis A. Lebret, E to provide support in the diagnosis of hydrocephalus, which requires an assessment to the volumes a fully automatic method to estimate the CSF volumes from a new 3D whole body MR imaging sequence

  3. Normal pressure hydrocephalus. Influences on cerebral hemodynamic and cerebrospinal fluid pressure--chemical autoregulation

    Microsoft Academic Search

    John S. Meyer; Hisao Tachibana; Jeffrey P. Hardenberg; Richard E. Dowell Jr.; Yasuhisa Kitagawa; Karl F. Mortel

    1984-01-01

    Blood flow in the cerebral gray matter was measured in normal pressure hydrocephalus and Alzheimer disease by 133Xe inhalation. Flow values in the frontal and temporal gray matter increased after lowering cerebrospinal fluid (CSF) pressure by lumbar puncture in normal pressure hydrocephalus (p less than 0.05) and also after shunting. One case with cerebral complications did not improve clinically. In

  4. Elevated nerve growth factor and neurotrophin-3 levels in cerebrospinal fluid of children with hydrocephalus

    Microsoft Academic Search

    Frederike Hochhaus; Petra Koehne; Christoph Schäper; Otfrid Butenandt; Ursula Felderhoff-Mueser; Elfride Ring-Mrozik; Michael Obladen; Christoph Bührer

    2001-01-01

    BACKGROUND: Elevated intracranial pressure (ICP) resulting from impaired drainage of cerebrospinal fluid (CSF) causes hydrocephalus with damage to the central nervous system. Clinical symptoms of elevated intracranial pressure (ICP) in infants may be difficult to diagnose, leading to delayed treatment by shunt placement. Until now, no biochemical marker of elevated ICP has been available for clinical diagnosis and monitoring. In

  5. Idiopathic normal pressure hydrocephalus: Analysis of factors related to cerebrospinal fluid dynamics determining functional prognosis

    Microsoft Academic Search

    A. Bfircena; C. Mestre; J. M. Cafiizal; B. Rivero; R. D. Lobato

    1997-01-01

    Summary This investigation has been undertaken to analyze the findings with both the cerebrospinal fluid (CSF) pressure (Pcsf) and CSF pulse pressure (PP) in order to predict the outcome of patients with the syndrome of idiopathic normal pressure hydrocephalus (NPH). Accordingly, a prospective clinical study was planned in which two groups of patients with NPH, having analogous prevalence of several

  6. Cerebrospinal fluid markers before and after shunting in patients with secondary and idiopathic normal pressure hydrocephalus

    Microsoft Academic Search

    Mats Tullberg; Kaj Blennow; Jan-Eric Månsson; Pam Fredman; Magnus Tisell; Carsten Wikkelsö

    2008-01-01

    BACKGROUND: The aim of this study was to explore biochemical changes in the cerebrospinal fluid (CSF) induced by shunt surgery and the relationship between these changes and clinical improvement. METHODS: We measured clinical symptoms and analysed lumbar CSF for protein content, neurodegeneration and neurotransmission markers in patients with secondary (SNPH, n = 17) and idiopathic NPH (INPH, n = 18)

  7. Proposal of “evolution theory in cerebrospinal fluid dynamics” and minor pathway hydrocephalus in developing immature brain

    Microsoft Academic Search

    Shizuo Oi; Concezio Di Rocco

    2006-01-01

    Background  The specificity of cerebrospinal fluid (CSF) dynamics in the immature brain still remains unknown. In our data previously published, the transependymal intraparenchymal CSF pathway (the minor pathway) plays a significant role in various degrees in the alternative CSF passage. Now, there is a growing consensus in the age differences in the outcome of neuroendoscopic ventriculostomy in treatment of non-communicating types

  8. Concentrations of albendazole in serum, cerebrospinal fluid and hydatidous brain cyst

    Microsoft Academic Search

    Dag Moskopp; Erich Lotterer

    1993-01-01

    A young girl with cerebral echinococcosis was treated with albendazole (13 mg\\/kg\\/d, p.o.). The concentrations of albendazole sulphoxide were determined in serum, cerebrospinal fluid and hydatidous cyst over a month. The mean ratios of concentration were: CSF\\/serum=50%, cyst\\/serum=40%, cyst\\/CSF=80%.

  9. Concentrations of albendazole in serum, cerebrospinal fluid and hydatidous brain cyst.

    PubMed

    Moskopp, D; Lotterer, E

    1993-01-01

    A young girl with cerebral echinococcosis was treated with albendazole (13 mg/kg/d, p.o.). The concentrations of albendazole sulphoxide were determined in serum, cerebrospinal fluid and hydatidous cyst over a month. The mean ratios of concentration were: CSF/serum = 50%, cyst/serum = 40%, cyst/CSF = 80%. PMID:8483517

  10. Antibodies against myelin oligodendrocyte glycoprotein in the cerebrospinal fluid of multiple sclerosis patients

    Microsoft Academic Search

    Milos Markovic; Vladimir Trajkovic; Jelena Drulovic; Sarlota Mesaros; Nebojsa Stojsavljevic; Irena Dujmovic; Marija Mostarica Stojkovic

    2003-01-01

    Antibodies against myelin oligodendrocyte glycoprotein (MOG) mediate demyelination in experimental autoimmune encephalomyelitis (EAE) in different animal species and are implicated in the immunopathogenesis of multiple sclerosis (MS). In order to evaluate the anti-MOG response, we have analyzed the cerebrospinal fluids (CSFs) from 44 MS patients and 51 controls, 11 with other inflammatory neurological disorders (OIND) and 40 with non-inflammatory neurological

  11. MR phase imaging and cerebrospinal fluid flow in the head and spine

    Microsoft Academic Search

    L. M. Levy; G. Di Chiro

    1990-01-01

    Motion of the cerebrospinal fluid (CSF) in and around the brain and spinal cord was examined in healthy subjects and in a number of patients with abnormalities of the CSF circulation. The pulsatile motion of the CSF was determined by spin echo phase (velocity) imaging, sometimes in combination with gradient echo phase contrast cine. Differences in flow patterns across CSF

  12. Clinical and Analytical Evaluation of an Enzyme Immunoassay for Myelin Basic Protein in Cerebrospinal Fluid

    Microsoft Academic Search

    Mitsuhiro Ohta; Kiyoe Ohta; Jie M; Juji Takeuchi; Takahiko Said; Masataka Nishimura; Nobuyuki Itoh

    Background: RIA of myelin basic protein (MBP) in cerebrospinal fluid (CSF) is commonly used as a bio- chemical marker of demyelination in patients with multiple sclerosis (MS). Our aim was to develop a sufficiently sensitive ELISA for MBP and evaluate it clinically in patients with MS. Methods: The ELISA used anti-bovine MBP antibody coated on plates and biotinylated anti-MBP antibody.

  13. Cerebrospinal fluid leak associated with nasal continuous positive airway pressure treatment for obstructive sleep apnoea

    Microsoft Academic Search

    Jean Yared; Jaafar El Annan

    2010-01-01

    Clear rhinorrhoea is a common symptom in patients with obstructive sleep apnoea (OSA), which may worsen with nasal continuous positive airway pressure treatment (nCPAP). However, rhinorrhoea can also be the presenting symptom of cerebrospinal fluid (CSF) leak, which is due to a communication between the subarachnoid space and the nasal cavity or sinuses. We report another case of a patient

  14. Measurement of lactate in cerebrospinal fluid in investigation of inherited metabolic disease

    Microsoft Academic Search

    Andrew Hutchesson; Mary Anne Preece; George Gray; Anne Green

    Measurement of lactate concentrations in cerebrospinal fluid (CSF) has been suggested as part of the investiga- tion of inborn errors of the electron transport chain, but little information exists regarding the reference range in children or the relationship between CSF and plasma concentrations. In 39 children without bacterial menin- gitis, diabetes, or recent seizures, we determined that the median (range)

  15. Abnormal Expression of Cerebrospinal Fluid Cation Chloride Cotransporters in Patients with Rett Syndrome

    PubMed Central

    Duarte, Sofia Temudo; Armstrong, Judith; Roche, Ana; Ortez, Carlos; Pérez, Ana; O’Callaghan, Maria del Mar; Pereira, Antonina; Sanmartí, Francesc; Ormazábal, Aida; Artuch, Rafael; Pineda, Mercedes; García-Cazorla, Angels

    2013-01-01

    Objective Rett Syndrome is a progressive neurodevelopmental disorder caused mainly by mutations in the gene encoding methyl-CpG-binding protein 2. The relevance of MeCP2 for GABAergic function was previously documented in animal models. In these models, animals show deficits in brain-derived neurotrophic factor, which is thought to contribute to the pathogenesis of this disease. Neuronal Cation Chloride Cotransporters (CCCs) play a key role in GABAergic neuronal maturation, and brain-derived neurotrophic factor is implicated in the regulation of CCCs expression during development. Our aim was to analyse the expression of two relevant CCCs, NKCC1 and KCC2, in the cerebrospinal fluid of Rett syndrome patients and compare it with a normal control group. Methods The presence of bumetanide sensitive NKCC1 and KCC2 was analysed in cerebrospinal fluid samples from a control pediatric population (1 day to 14 years of life) and from Rett syndrome patients (2 to 19 years of life), by immunoblot analysis. Results Both proteins were detected in the cerebrospinal fluid and their levels are higher in the early postnatal period. However, Rett syndrome patients showed significantly reduced levels of KCC2 and KCC2/NKCC1 ratio when compared to the control group. Conclusions Reduced KCC2/NKCC1 ratio in the cerebrospinal fluid of Rett Syndrome patients suggests a disturbed process of GABAergic neuronal maturation and open up a new therapeutic perspective. PMID:23894354

  16. Cerebrospinal fluid GABA levels in chronic migraine with and without depression

    Microsoft Academic Search

    D. S. S. Vieira; M. G. Naffah-Mazacoratti; E. Zukerman; C. A. Senne Soares; E. O. Alonso; M. H. W. Faulhaber; E. A. Cavalheiro; M. F. P. Peres

    2006-01-01

    Psychiatric comorbidity is one of the key elements in chronic migraine (CM) management. Depression is particularly common in these patients, occurring in up to 85%. Preclinical studies have suggested that gamma-aminobutyric acid (GABA) levels may be decreased in animal models of depression. Also, clinical studies have reported low level in mood disorder patients for both plasma and cerebrospinal fluid (CSF)

  17. Increased adrenomedullin in cerebrospinal fluid after traumatic brain injury in infants and children.

    PubMed

    Robertson, C L; Minamino, N; Ruppel, R A; Kangawa, K; Wisniewski, S R; Tsuji, T; Janesko, K L; Ohta, H; Adelson, P D; Marion, D W; Kochanek, P M

    2001-09-01

    Adrenomedullin is a recently discovered 52-amino acid peptide that is a potent vasodilator and is produced in the brain in experimental models of cerebral ischemia. Infusion of adrenomedullin increases regional cerebral blood flow and reduces infarct volume after vascular occlusion in rats, and thus may represent an endogenous neuroprotectant. Disturbances in cerebral blood flow (CBF), including hypoperfusion and hyperemia, frequently occur after severe traumatic brain injury (TBI) in infants and children. We hypothesized that cerebrospinal fluid (CSF) adrenomedullin concentration would be increased after severe TBI in infants and children, and that increases in adrenomedullin would be associated with alterations in CBF. We also investigated whether posttraumatic CSF adrenomedullin concentration was associated with relevant clinical variables (CBF, age, Glasgow Coma Scale [GCS] score, mechanism of injury, and outcome). Total adrenomedullin concentration was measured using a radioimmunometric assay. Sixty-six samples of ventricular CSF from 21 pediatric patients were collected during the first 10 days after severe TBI (GCS score < 8). Control CSF was obtained from children (n = 10) undergoing lumbar puncture without TBI or meningitis. Patients received standard neurointensive care, including CSF drainage. CBF was measured using Xenon computed tomography (CT) in 11 of 21 patients. Adrenomedullin concentration was markedly increased in CSF of infants and children after severe TBI vs control (median 4.5 versus 1.0 fmol/mL, p < 0.05). Sixty-two of 66 CSF samples (93.9%) from head-injured infants and children had a total adrenomedullin concentration that was greater than the median value for controls. Increases in CSF adrenomedullin were most commonly observed early after TBI. CBF was positively correlated with CSF adrenomedullin concentration (p < 0.001), but this relationship was not significant when controlling for the effect of time. CSF adrenomedullin was not significantly associated with other selected clinical variables. We conclude adrenomedullin is markedly increased in the CSF of infants and children early after severe TBI. We speculate that adrenomedullin participates in the regulation of CBF after severe TBI. PMID:11565598

  18. Delayed presentation of late-onset cerebrospinal fluid rhinorrhoea following dopamine agonist therapy for giant prolactinoma

    PubMed Central

    Prague, J K; Ward, C L; Mustafa, O G; King, A; Thomas, N W; Gilbert, J

    2014-01-01

    Summary Therapeutic shrinkage of prolactinomas with dopamine agonists achieves clinical benefit but can expose fistulae that have arisen as a result of bony erosion of the sella floor and anterior skull base by the invasive tumour, resulting in the potential development of cerebrospinal fluid (CSF) rhinorrhoea, meningitis, and rarely pneumocephalus. Onset of symptoms is typically within 4 months of commencing therapy. The management is typically surgical repair via an endoscopic transnasal transsphenoidal approach. A 23-year-old man presented to the Emergency Department with acute left limb weakness and intermittent headaches. Visual fields were full to confrontation. Immediate computed tomography and subsequent magnetic resonance imaging (MRI), demonstrated a 5?cm lobular/cystic mass invading the right cavernous sinus, displacing and compressing the midbrain, with destruction of the bony sella. He was referred to the regional pituitary multidisciplinary team (MDT). Serum prolactin was 159?455?mIU/l (7514.37?ng/ml) (normal ranges 100–410?mIU/l (4.72–19.34?ng/ml)). Cabergoline was commenced causing dramatic reduction in tumour size and resolution of neurological symptoms. Further dose titrations were required as the prolactin level plateaued and significant residual tumour remained. After 13 months of treatment, he developed continuous daily rhinorrhea, and on presenting to his general practitioner was referred to an otolaryngologist. When next seen in the routine regional pituitary clinic six-months later he was admitted for urgent surgical repair. Histology confirmed a prolactinoma with a low proliferation index of 2% (Ki-67 antibody). In view of partial cabergoline resistance he completed a course of conventional radiotherapy. Nine months after treatment the serum prolactin had fallen to 621?mIU/l, and 12 months after an MRI showed reduced tumour volume. Learning points CSF rhinorrhoea occurred 13 months after the initiation of cabergoline, suggesting a need for vigilance throughout therapy.Dedicated bony imaging should be reviewed early in the patient pathway to assess the potential risk of CSF rhinorrhoea after initiation of dopamine agonist therapy.There was a significant delay before this complication was brought to the attention of the regional pituitary MDT, with associated risk whilst left untreated. This demonstrates a need for patients and healthcare professionals to be educated about early recognition and management of this complication to facilitate timely and appropriate referral to the MDT for specialist advice and management. We changed our nurse-led patient education programme as a result of this case.An excellent therapeutic response was achieved with conventional radiotherapy after limited surgery having developed partial cabergoline resistance and CSF rhinorrhoea. PMID:25520847

  19. Human Cardioviruses, Meningitis, and Sudden Infant Death Syndrome in Children

    PubMed Central

    Drexler, Jan Felix; Baumgarte, Sigrid; Eschbach-Bludau, Monika; Simon, Arne; Kemen, Christoph; Bode, Udo; Eis-Hübinger, Anna-Maria; Madea, Burkhard

    2011-01-01

    Cardioviruses cause myocarditis and encephalomyelitis in rodents; human cardioviruses have not been ascribed to any disease. We screened 6,854 cerebrospinal fluid and 10 myocardium specimens from children and adults. A genotype 2 cardiovirus was detected from a child who died of sudden infant death syndrome, and 2 untypeable cardioviruses were detected from 2 children with meningitis. PMID:22153118

  20. Streptococcal Meningitis Resulting from Contact with an Infected Horse

    PubMed Central

    Downar, James; Willey, Barbara M.; Sutherland, Jeffrey W.; Mathew, Kelly; Low, Donald E.

    2001-01-01

    We report a case of group C streptococcal meningitis in a woman with a history of close animal contact as well as head trauma as a result of a kick by a horse. Blood and cerebrospinal fluid cultures grew Streptococcus equi subsp. zooepidemicus, as did a throat culture taken from the colt that had kicked her 2 weeks prior to admission. PMID:11376093

  1. Cerebrospinal Fluid from Patients with Subarachnoid Haemorrhage and Vasospasm Enhances Endothelin Contraction in Rat Cerebral Arteries

    PubMed Central

    Assenzio, Barbara; Martin, Erica L.; Stankevicius, Edgaras; Civiletti, Federica; Fontanella, Marco; Boccaletti, Riccardo; Berardino, Maurizio; Mazzeo, AnnaTeresa; Ducati, Alessandro; Simonsen, Ulf; Mascia, Luciana

    2015-01-01

    Introduction Previous studies have suggested that cerebrospinal fluid from patients with subarachnoid hemorrhage (SAH) leads to pronounced vasoconstriction in isolated arteries. We hypothesized that only cerebrospinal fluid from SAH patients with vasospasm would produce an enhanced contractile response to endothelin-1 in rat cerebral arteries, involving both endothelin ETA and ETB receptors. Methods Intact rat basilar arteries were incubated for 24 hours with cerebrospinal fluid from 1) SAH patients with vasospasm, 2) SAH patients without vasospasm, and 3) control patients. Arterial segments with and without endothelium were mounted in myographs and concentration-response curves for endothelin-1 were constructed in the absence and presence of selective and combined ETA and ETB receptor antagonists. Endothelin concentrations in culture medium and receptor expression were measured. Results Compared to the other groups, the following was observed in arteries exposed to cerebrospinal fluid from patients with vasospasm: 1) larger contractions at lower endothelin concentrations (p<0.05); 2) the increased endothelin contraction was absent in arteries without endothelium; 3) higher levels of endothelin secretion in the culture medium (p<0.05); 4) there was expression of ETA receptors and new expression of ETB receptors was apparent; 5) reduction in the enhanced response to endothelin after ETB blockade in the low range and after ETA blockade in the high range of endothelin concentrations; 6) after combined ETA and ETB blockade a complete inhibition of endothelin contraction was observed. Conclusions Our experimental findings showed that in intact rat basilar arteries exposed to cerebrospinal fluid from patients with vasospasm endothelin contraction was enhanced in an endothelium-dependent manner and was blocked by combined ETA and ETB receptor antagonism. Therefore we suggest that combined blockade of both receptors may play a role in counteracting vasospasm in patients with SAH. PMID:25629621

  2. Monoaminc and metabolite levels in the cerebrospinal fluid of hibernating and euthermic marmots.

    PubMed

    Reid; Kilduff; Romero; Florant; Dement; Heller

    1992-03-01

    Cerebrospinal fluid from yellow-bellied marmots, Marmota flaviventris, was analysed for monoamine and monoamine metabolite content during euthermia and deep hibernation. Dopamine (DA) levels were decreased, while DA metabolite levels, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were dramatically increased in hibernating marmots. Serotonin (5-HT) and 5-hydroxyindoleacetic acid (5HIAA) levels were also greatly enhanced during hibernation while norepinephrine (NE) levels were only moderately increased. These findings demonstrate that cerebrospinal monoamine levels are dynamically altered during hibernation, such that DA versus 5-HT and NE levels undergo opposite changes. Therefore, these data indicate that DA, 5-HT and NE neuronal systems are differentially altered during hibernation in mammals. PMID:10607025

  3. Multiplicity of cerebrospinal fluid functions: New challenges in health and disease

    Microsoft Academic Search

    Conrad E Johanson; John A Duncan III; Petra M Klinge; Thomas Brinker; Edward G Stopa; Gerald D Silverberg

    2008-01-01

    This review integrates eight aspects of cerebrospinal fluid (CSF) circulatory dynamics: formation rate, pressure, flow, volume, turnover rate, composition, recycling and reabsorption. Novel ways to modulate CSF formation emanate from recent analyses of choroid plexus transcription factors (E2F5), ion transporters (NaHCO3 cotransport), transport enzymes (isoforms of carbonic anhydrase), aquaporin 1 regulation, and plasticity of receptors for fluid-regulating neuropeptides. A greater

  4. [Pasteurella multocida meningitis with cerebral abscesses].

    PubMed

    Nguefack, S; Moifo, B; Chiabi, A; Mah, E; Bogne, J-B; Fossi, M; Fru, F; Mbonda, E; Djientcheu, V-P

    2014-03-01

    Pasteurella multocida is classically responsible for local soft tissue infections secondary to dog bites or cat scratches. It can be responsible for meningitis in infants and elderly persons. We report the case history of a 5-year-old male child admitted to our pediatric unit for meningitis. Cerebrospinal fluid analysis revealed an infection with P. multocida. The suspected mode of contamination was either from the saliva of a pet dog or through an unnoticed skull fracture sustained after an accident 1 year prior to the occurrence of meningitis. In spite of the neurologic complication (cerebral abscess), the progression was favorable after drainage of the abscess, 5 weeks of parenteral treatment, and 3 weeks of oral antibiotic therapy. Meningitis due to Pasteurella sp. is rare and can lead to neurologic complications. The notion of bites or scratches can be absent and the mode of contamination is sometimes difficult to unveil. PMID:24457110

  5. A case of presumably Rathke's cleft cyst associated with postoperative cerebrospinal fluid leakage through persisting embryonal infundibular recess.

    PubMed

    Kuroiwa, Masafumi; Kusano, Yoshikazu; Ogiwara, Toshihiro; Tanaka, Yuichiro; Takemae, Toshiki; Hongo, Kazuhiro

    2014-01-01

    Persisting embryonal infundibular recess (PEIR) is a rare anomaly of the third ventricular floor. Only eight cases have been published. In this report, a case of presumably Rathke's cleft cyst associated with cerebrospinal fluid leakage caused by PEIR is described. An 81-year-old woman underwent endoscopic transsphenoidal surgery for the intra- and supra-sellar cystic lesion. Intraoperatively a hole was confirmed over the sella turcica connecting the sellar cyst and the infundibular recess. Liquorrhea did not occur throughout the procedure. A computed tomography (CT) scan obtained immediately after surgery disclosed accumulation of air in the third and lateral ventricles, in addition to the intra- and supra-sellar region. Air accumulation resolved spontaneously after bed rest for 11 days and she was discharged without neurological deficits. However, she required the second transsphenoidal surgery to repair the sellar floor because of bacterial meningitis caused by liquorrhea on the postoperative day 23. A postoperative 3-tesla magnetic resonance image revealed a deep infundibular recess connecting the sella turcica and the third ventricle, which was considered to be PEIR. To the best our knowledge, this is the first reported case describing the intraoperative findings of PEIR. PMID:24305020

  6. Osmotic demyelination and hypertonic dehydration in a 9-year-old girl: changes in cerebrospinal fluid myelin basic protein.

    PubMed

    Shah, Bobby; Tobias, Joseph D

    2006-01-01

    A 9-year-old girl was admitted for the treatment of hyper-natremic dehydration. Her history was significant for psychogenic polydipsia, hyponatremia, and a renal concentrating defect. She presented with a 2-day history of altered mental status, ataxia, lethargy, fever, nausea, vomiting, and diarrhea. Meningitis was ruled out. Over the course of her illness, slow rehydration was maintained with a gradual decrease (10 mEq per 24 hours) of the serum sodium. Despite this care, she developed quadriparesis, and magnetic resonance imaging performed on day 6 of her illness was consistent with osmotic demyelination (central pontine myelinolysis). To rule out an excessively rapid correction of hypernatremia as the etiology of the problem, a myelin basic protein was measured in the cerebrospinal fluid that had been obtained on hospital day 1. The myelin basic protein was 649.50 ng/mL (normal, 0.07-4.10 ng/mL). The current literature is presented regarding the postulated pathogenesis of central pontine myelinolysis and suggested therapies, previous reports of central pontine myelinolysis in children are reviewed, and the potential role of myelin basic protein in its diagnosis is discussed. PMID:17095502

  7. A Novel Unbiased Proteomic Approach to Detect the Reactivity of Cerebrospinal Fluid in Neurological Diseases*

    PubMed Central

    Menon, Krishnakumar N.; Steer, David L.; Short, Martin; Petratos, Steven; Smith, Ian; Bernard, Claude C. A.

    2011-01-01

    Neurodegenerative diseases, such as multiple sclerosis represent global health issues. Accordingly, there is an urgent need to understand the pathogenesis of this and other central nervous system disorders, so that more effective therapeutics can be developed. Cerebrospinal fluid is a potential source of important reporter molecules released from various cell types as a result of central nervous system pathology. Here, we report the development of an unbiased approach for the detection of reactive cerebrospinal fluid molecules and target brain proteins from patients with multiple sclerosis. To help identify molecules that may serve as clinical biomarkers for multiple sclerosis, we have biotinylated proteins present in the cerebrospinal fluid and tested their reactivity against brain homogenate as well as myelin and myelin-axolemmal complexes. Proteins were separated by two-dimensional gel electrophoresis, blotted onto membranes and probed separately with biotinylated unprocessed cerebrospinal fluid samples. Protein spots that reacted to two or more multiple sclerosis-cerebrospinal fluids were further analyzed by matrix assisted laser desorption ionization-time-of-flight time-of-flight mass spectrometry. In addition to previously reported proteins found in multiple sclerosis cerebrospinal fluid, such as ?? crystallin, enolase, and 14–3-3-protein, we have identified several additional molecules involved in mitochondrial and energy metabolism, myelin gene expression and/or cytoskeletal organization. These include aspartate aminotransferase, cyclophilin-A, quaking protein, collapsin response mediator protein-2, ubiquitin carboxy-terminal hydrolase L1, and cofilin. To further validate these findings, the cellular expression pattern of collapsin response mediator protein-2 and ubiquitin carboxy-terminal hydrolase L1 were investigated in human chronic-active MS lesions by immunohistochemistry. The observation that in multiple sclerosis lesions phosphorylated collapsin response mediator protein-2 was increased, whereas Ubiquitin carboxy-terminal hydrolase L1 was down-regulated, not only highlights the importance of these molecules in the pathology of this disease, but also illustrates the use of our approach in attempting to decipher the complex pathological processes leading to multiple sclerosis and other neurodegenerative diseases. PMID:21421798

  8. Unusual cause of fatal anthrax meningitis.

    PubMed

    Parlak, Emine; Parlak, Mehmet; Atli, Seval Bilgiç

    2015-03-01

    We report the case of fatal anthrax meningoencephalitis in the province of Mu? located in eastern Anatolia, Turkey. The organism isolated from cerebrospinal fluid was identified as Bacillus anthracis. The patient was treated with crystallized penicillin G (24 MU/day IV) and ciprofloxacin (2?×?400/day IV), but died 5 days after hospitalization. Although it is a rare case, we consider that the patients who have skin, respiratory and neurological systems might also have hemorrhagic meningitis. PMID:24678752

  9. Postmortem Cerebrospinal Fluid Pleocytosis: A Marker of Inflammation or Postmortem Artifact?

    PubMed Central

    Morris, James A.; Harrison, Linda M.; Telford, David R.

    2012-01-01

    The aim of this paper is to reassess the significance of postmortem cerebrospinal fluid pleocytosis. Published articles of CSF changes after death were reviewed, and reanalysis, in the light of modern views on the significance of bacterial postmortem isolates, was undertaken. There is theoretical and experimental evidence that the blood brain barrier to the movement of protein and cells is preserved in the first few hours after death. The number of mononuclear cells in the cerebrospinal fluid does rise in the first 24 hours after death, and this is most probably due to detachment of leptomeningeal lining cells. But the marked increase in lymphocyte counts seen in some cases of sudden infant death syndrome (SIDS) and in other deaths in the paediatric age range could well be a marker of inflammation. PMID:22518189

  10. Increased selenoprotein P in choroid plexus and cerebrospinal fluid in Alzheimer's disease brain.

    PubMed

    Rueli, Rachel H L H; Parubrub, Arlene C; Dewing, Andrea S T; Hashimoto, Ann C; Bellinger, Miyoko T; Weeber, Edwin J; Uyehara-Lock, Jane H; White, Lon R; Berry, Marla J; Bellinger, Frederick P

    2015-01-01

    Subjects with Alzheimer's disease (AD) have elevated brain levels of the selenium transporter selenoprotein P (Sepp1). We investigated if this elevation results from increased release of Sepp1 from the choroid plexus (CP). Sepp1 is significantly increased in CP from AD brains in comparison to non-AD brains. Sepp1 localizes to the trans-Golgi network within CP epithelia, where it is processed for secretion. The cerebrospinal fluid from AD subjects also contains increased levels Sepp1 in comparison to non-AD subjects. These findings suggest that AD pathology induces increased levels of Sepp1 within CP epithelia for release into the cerebrospinal fluid to ultimately increase brain selenium. PMID:25298198

  11. Th1 polarization of T cells injected into the cerebrospinal fluid induces brain immunosurveillance.

    PubMed

    Fisher, Yair; Strominger, Itai; Biton, Shva; Nemirovsky, Anna; Baron, Rona; Monsonego, Alon

    2014-01-01

    Although CD4 T cells reside within the cerebrospinal fluid, it is yet unclear whether and how they enter the brain parenchyma and migrate to target specific Ags. We examined the ability of Th1, Th2, and Th17 CD4 T cells injected intracerebroventricularly to migrate from the lateral ventricles into the brain parenchyma in mice. We show that primarily Th1 cells cross the ependymal layer of the ventricle and migrate within the brain parenchyma by stimulating an IFN-?-dependent dialogue with neural cells, which maintains the effector function of the T cells. When injected into a mouse model of Alzheimer's disease, amyloid-? (A?)-specific Th1 cells target A? plaques, increase A? uptake, and promote neurogenesis with no evidence of pathogenic autoimmunity or neuronal loss. Overall, we provide a mechanistic insight to the migration of cerebrospinal fluid CD4 T cells into the brain parenchyma and highlight implications on brain immunity and repair. PMID:24307730

  12. Postsurgical Pantoea calida meningitis: a case report

    PubMed Central

    2014-01-01

    Introduction Pantoea calida, a recently described environmental Enterobacteriaceae organism, has not yet been associated with human infection. Case presentation We report a case of postoperative meningitis caused by P. calida. After pituitary adenoma resection, a 52-year-old Caucasian woman developed febrile meningitis confirmed by cerebrospinal fluid analysis. P. calida was grown in pure culture from this fluid and was firmly identified with partial rpoB gene sequencing. She was cured by a 14-day course of meropenem. Conclusions P. calida must be added to the list of opportunistic Enterobacteriaceae pathogens responsible for postsurgical meningitis. It is easily identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. PMID:24934580

  13. A simplified radioimmunological method for the determination of human ?-endorphin in cerebrospinal fluid

    Microsoft Academic Search

    H. Przuntek; J.-P. Stasch; M. Graf; K. W. Pflughaupt; N. Gropp; M. Witteler

    1981-01-01

    Human ?-endorphin-like immunoreactive substances (?h-EI) in human cerebrospinal fluid (CSF) were determined radioimmunologically. The cross reactivity of the antibodies to human ?-endorphin (?h-E) amounted to 40% for human ?-lipotropin (?h-LPH) whilst it was less than 1% for leu-and metenkephalin, ?- and ?-endorphin, fraction I and II [5], substance P and ?-MSH. Prior to radioimmunological determination, an adsorbtion of ?h-EI from

  14. Factors influencing the measurement of lysosomal enzymes activity in human cerebrospinal fluid.

    PubMed

    Persichetti, Emanuele; Chiasserini, Davide; Parnetti, Lucilla; Eusebi, Paolo; Paciotti, Silvia; De Carlo, Claudia; Codini, Michela; Tambasco, Nicola; Rossi, Aroldo; El Agnaf, Omar M; Calabresi, Paolo; Beccari, Tommaso

    2014-01-01

    Measurements of the activities of lysosomal enzymes in cerebrospinal fluid have recently been proposed as putative biomarkers for Parkinson's disease and other synucleinopathies. To define the operating procedures useful for ensuring the reliability of these measurements, we analyzed several pre-analytical factors that may influence the activity of ?-glucocerebrosidase, ?-mannosidase, ?-mannosidase, ?-galactosidase, ?-fucosidase, ?-hexosaminidase, cathepsin D and cathepsin E in cerebrospinal fluid. Lysosomal enzyme activities were measured by well-established fluorimetric assays in a consecutive series of patients (n?=?28) with different neurological conditions, including Parkinson's disease. The precision, pre-storage and storage conditions, and freeze/thaw cycles were evaluated. All of the assays showed within- and between-run variabilities below 10%. At -20°C, only cathepsin D was stable up to 40 weeks. At -80°C, the cathepsin D, cathepsin E, and ?-mannosidase activities did not change significantly up to 40 weeks, while ?-glucocerebrosidase activity was stable up to 32 weeks. The ?-galactosidase and ?-fucosidase activities significantly increased (+54.9±38.08% after 4 weeks and +88.94±36.19% after 16 weeks, respectively). Up to four freeze/thaw cycles did not significantly affect the activities of cathepsins D and E. The ?-glucocerebrosidase activity showed a slight decrease (-14.6%) after two freeze/thaw cycles. The measurement of lysosomal enzyme activities in cerebrospinal fluid is reliable and reproducible if pre-analytical factors are accurately taken into consideration. Therefore, the analytical recommendations that ensue from this study may contribute to the establishment of actual values for the activities of cerebrospinal fluid lysosomal enzymes as putative biomarkers for Parkinson's disease and other neurodegenerative disorders. PMID:24983953

  15. Postoperative Cerebrospinal Fluid Leaks of the Lumbosacral Spine: Management with Percutaneous Fibrin Glue

    Microsoft Academic Search

    Mahesh R. Patel; William Louie; Jacob Rachlin

    PURPOSE: To assess CT-guided injection of fibrin glue for the management of lumbosacral cerebrospinal fluid (CSF) leaks.METHODS:Six consecutive patients with postoperative CSF leaks were treated after CSF aspiration under CT guidance. A solution of cryoprecipitate was simulta- neously injected with a 10% calcium chloride solution containing 2000 units of thrombin per milliliter. In one patient, 0.5 mL of iopamidol was

  16. Osmotic Mechanisms Regulating Cerebrospinal Fluid Vasopressin and Oxytocin in the Conscious Rat

    Microsoft Academic Search

    Mariana Morris; Ralph Roger Barnard Jr; Larry E. Sain

    1984-01-01

    The effect of intraventricular and intravenous (i.v.) hypertonic saline on plasma and perfusate arginine vasopressin (AVP) and oxytocin (OT) levels was determined. A push-pull technique was used to sample third ventricular cerebrospinal fluid (CSF) in the conscious unrestrained rat. Intraventricular perfusion of hypertonic saline caused a 6.1-and 4.2-fold increase in perfusate levels of AVP and OT. Plasma levels with the

  17. Computer modelling of the cerebrospinal fluid flow dynamics of aqueduct stenosis

    Microsoft Academic Search

    E. E. Jacobson; D. F. Fletcher; M. K. Morgan; I. H. Johnston

    1999-01-01

    As the craniospinal space is a pressure loaded system it is difficult to conceptualise and understand the flow dynamics through\\u000a the ventricular system. Aqueduct stenosis compromises flow, increasing the pressure required to move cerebrospinal fluid (CSF)\\u000a through the ventricles. Under normal circumstances, less than one pascal (1Pa) of pressure is required to move a physiological\\u000a flow of CSF through the

  18. Factors Influencing the Measurement of Lysosomal Enzymes Activity in Human Cerebrospinal Fluid

    PubMed Central

    Parnetti, Lucilla; Eusebi, Paolo; Paciotti, Silvia; De Carlo, Claudia; Codini, Michela; Tambasco, Nicola; Rossi, Aroldo; Agnaf, Omar M. El.; Calabresi, Paolo; Beccari, Tommaso

    2014-01-01

    Measurements of the activities of lysosomal enzymes in cerebrospinal fluid have recently been proposed as putative biomarkers for Parkinson's disease and other synucleinopathies. To define the operating procedures useful for ensuring the reliability of these measurements, we analyzed several pre-analytical factors that may influence the activity of ?-glucocerebrosidase, ?-mannosidase, ?-mannosidase, ?-galactosidase, ?-fucosidase, ?-hexosaminidase, cathepsin D and cathepsin E in cerebrospinal fluid. Lysosomal enzyme activities were measured by well-established fluorimetric assays in a consecutive series of patients (n?=?28) with different neurological conditions, including Parkinson's disease. The precision, pre-storage and storage conditions, and freeze/thaw cycles were evaluated. All of the assays showed within- and between-run variabilities below 10%. At ?20°C, only cathepsin D was stable up to 40 weeks. At ?80°C, the cathepsin D, cathepsin E, and ?-mannosidase activities did not change significantly up to 40 weeks, while ?-glucocerebrosidase activity was stable up to 32 weeks. The ?-galactosidase and ?-fucosidase activities significantly increased (+54.9±38.08% after 4 weeks and +88.94±36.19% after 16 weeks, respectively). Up to four freeze/thaw cycles did not significantly affect the activities of cathepsins D and E. The ?-glucocerebrosidase activity showed a slight decrease (?14.6%) after two freeze/thaw cycles. The measurement of lysosomal enzyme activities in cerebrospinal fluid is reliable and reproducible if pre-analytical factors are accurately taken into consideration. Therefore, the analytical recommendations that ensue from this study may contribute to the establishment of actual values for the activities of cerebrospinal fluid lysosomal enzymes as putative biomarkers for Parkinson's disease and other neurodegenerative disorders. PMID:24983953

  19. Intracranial Hypotension Caused by Cervical Cerebrospinal Fluid Leak: Treatment with Epidural Blood Patch

    Microsoft Academic Search

    Michael J. Cousins; David Brazier; Raymond Cook

    2004-01-01

    This report describes treatment with cervical epidural blood patch of low cerebrospinal fluid (CSF) pressure headache resulting from spontaneous CSF leak via a tear in a cervical dural cuff. The leak was diagnosed by a dynamic computed tomography (CT)-myelography study followed by gadolinium enhanced magnetic res- onance imaging(MRI)-scan. The epidural needle was inserted with the aid of image intensifier and

  20. Hallucinogenic N-methylated indolealkylamines in the cerebrospinal fluid of psychiatric and control populations.

    PubMed

    Corbett, L; Christian, S T; Morin, R D; Benington, F; Smythies, J R

    1978-02-01

    The incidence and quantities of dimethyltryptamine and O-methylbufotenine were studied in the cerebrospinal fluid of patients suffering acute schizophrenic illnesses and in surgical and neurological control groups. Some schizophrenic patients have higher levels of both amines than do controls, though the differences in distribution did not reach statistical significance in the sample studied. The gas-chromatographic technique used is sensitive at the low picogram level. PMID:272218

  1. The blood–brain and the blood–cerebrospinal fluid barriers: function and dysfunction

    Microsoft Academic Search

    Britta Engelhardt; Lydia Sorokin

    2009-01-01

    The central nervous system (CNS) is tightly sealed from the changeable milieu of blood by the blood–brain barrier (BBB) and\\u000a the blood–cerebrospinal fluid (CSF) barrier (BCSFB). While the BBB is considered to be localized at the level of the endothelial\\u000a cells within CNS microvessels, the BCSFB is established by choroid plexus epithelial cells. The BBB inhibits the free paracellular\\u000a diffusion

  2. Serum and cerebrospinal fluid concentrations of melatonin: a pilot study in healthy male volunteers

    Microsoft Academic Search

    A. Rousseau; S. Petrén; J. Plannthin; T. Eklundh; C. Nordin

    1999-01-01

    Summary.   Melatonin was determined in serum and cerebrospinal fluid (CSF) obtained from 13 healthy males lumbar-punctured in the sitting\\u000a position without preceding bed rest.\\u000a \\u000a There was a significant correlation between the levels of melatonin in serum and the CSF.\\u000a \\u000a \\u000a The serum concentration was lower than that in the CSF, a finding that calls in question the theory that melatonin is

  3. Detection of cancer cells in the cerebrospinal fluid: current methods and future directions

    Microsoft Academic Search

    Cody L Weston; Michael J Glantz; James R Connor

    2011-01-01

    The spread of cancer into the central nervous system is a serious problem leading to neurological symptoms and rapid mortality.\\u000a The current tools available for detecting the spread of cancer into the cerebrospinal fluid (CSF) are cytology, neurologic\\u000a examination, and neuroimaging. All three of these methods can be applied in concert to reach a diagnosis, but they all suffer\\u000a from

  4. Influence of a polymeric formulation of ketoprofen on its diffusion into cerebrospinal fluid in rats

    Microsoft Academic Search

    M Matoga; F Péhourcq; F Lagrange; F Fawaz; B Bannwarth

    2002-01-01

    Poly(d,l)lactide nanocapsules (NCs) have been proposed as an alternative carrier for many drugs. We investigated the influence of this formulation on the pharmacokinetics of ketoprofen in the plasma and cerebrospinal fluid (CSF). Male Wistar rats were given intraperitoneal dose of ketoprofen (5 mg\\/kg) in a suspension of NCs or in a carboxymethylcellulose (CMC) solution (reference preparation). Blood and CSF samples

  5. Radioimmunoassay of serotonin (5-hydroxytryptamine) in cerebrospinal fluid, plasma, and serum

    SciTech Connect

    Engbaek, F.; Voldby, B

    1982-04-01

    A direct radioimmunoassay is described for serotonin (5-hydroxytryptamine) in cerebrospinal fluid, platelet-poor plasma, and serum. Antisera in rabbits was raised against serotonin diazotized to a conjugate of bovine albumin and D,L-p-aminophenylalanine. Polyethylene glycol, alone or in combination with anti-rabbit immunoglobulins, is used to separate bound and unbound tritiated serotonin. The minimum concentration of serotonin detectable is 2 nmol/L in a 200-..mu..L sample. Within-day precision (CV) is 4.3% between-day precision 7.7%. Analytical recoveries of serotonin are 109% and 101% for cerebrospinal fluid and plasma, respectively. Tryptophan, 5-hydroxytryptophan, 5-hydroxyindoleacetic acid, and 5-hydroxytryptophol do not interfere with the assay. However, 5-methoxytryptamine and tryptamine cross react. Of samples of cerebrospinal fluid from patients with disc herniations (n=21) or low-pressure hydrocephalus (n=10), one-third had concentrations of 2-4 nmol/L and two-thirds were below the minimum detectable concentration. The observed range for the concentration of serotonin in plasma of 14 normal subjects was 5-14 nmol/L (mean +/- SD, 9 +/- 3 nmol/L). The observed ranges for serotonin in serum were: for 10 women 520-900 (mean +/- SD: 695 +/- 110) nmol/L and for 10 men 380-680 (520 +/- 94) nmol/L.

  6. Development of a theoretical framework for analyzing cerebrospinal fluid dynamics

    PubMed Central

    Cohen, Benjamin; Voorhees, Abram; Vedel, Søren; Wei, Timothy

    2009-01-01

    Background To date hydrocephalus researchers acknowledge the need for rigorous but utilitarian fluid mechanics understanding and methodologies in studying normal and hydrocephalic intracranial dynamics. Pressure volume models and electric circuit analogs introduced pressure into volume conservation; but control volume analysis enforces independent conditions on pressure and volume. Previously, utilization of clinical measurements has been limited to understanding of the relative amplitude and timing of flow, volume and pressure waveforms; qualitative approaches without a clear framework for meaningful quantitative comparison. Methods Control volume analysis is presented to introduce the reader to the theoretical background of this foundational fluid mechanics technique for application to general control volumes. This approach is able to directly incorporate the diverse measurements obtained by clinicians to better elucidate intracranial dynamics and progression to disorder. Results Several examples of meaningful intracranial control volumes and the particular measurement sets needed for the analysis are discussed. Conclusion Control volume analysis provides a framework to guide the type and location of measurements and also a way to interpret the resulting data within a fundamental fluid physics analysis. PMID:19772652

  7. An inexpensive sedimentation chamber for the preparation of cytologic specimens of cerebrospinal fluid.

    PubMed

    Garma-Aviña, Armando

    2004-11-01

    An inexpensive sedimentation chamber to obtain cytologic specimens of cerebrospinal fluid (CSF) is described. The device, which has a total cost of about $5.00 can be built in few minutes. The device permits the cytologic study of specimens of CSF in clinics, where because of economic constraints, a cytocentrifuge is not available. The device permits the study of the CSF cells on either air-dried or wet smears even under field conditions, and the results obtained are consistent. Also, the device permits to retrieve the cell-free fluid for its use in chemical or immunologic procedures. PMID:15586578

  8. Cerebrospinal fluid (CSF) transient responses induced by hypercapnia

    SciTech Connect

    Fisher, M.J.

    1984-01-01

    CSF transient responses to CO/sub 2/ inhalation were measured before and after facilitated perfusate flow through subarachnoid spaces of anesthetized cats during ventriculocisternal perfusion with artificial CSF containing /sup 14/C-dextran. Convective mixing of perfusate in subarachnoid spaces was augmented while infusion constant, either by impeding cisternal efflux of perfusate by raising the cisternal outflow cannula (high CSF pressure), or by preventing CSF outflow by clamping the cisternal outflow cannula (stopflow; S-F). CSF transients were also measured before and after systemic administration of phenoxybenzamine (PBZ) in order to evaluate the contribution of sympatho-adrenergic activity to craniospinal CSF redistribution and mixing. Results from high CSF pressure and S-F experiments indicate that unequilibrated CSF contributes significantly to the reduced tracer concentration in CSF volume (Vd) since SCF effluent tracer concentration (Cd) was decreased after subarachnoid facilitated flow. Further, results from S-F studies indicate that at least 50% of Cd is due to craniospinal fluid redistribution, a process which, along with CSF outflow transients, was unaffected by PBZ. Conversely, PBZ administration decreased steady state SCF formation and absorption through alpha-mediated cerebrovascular responses and/or through beta-adrenoceptor inhibition of metabolism of CSF secretory epithelium.

  9. Transmigration of polymorphnuclear neutrophils and monocytes through the human blood-cerebrospinal fluid barrier after bacterial infection in vitro

    PubMed Central

    2013-01-01

    Background Bacterial invasion through the blood-cerebrospinal fluid barrier (BCSFB) during bacterial meningitis causes secretion of proinflammatory cytokines/chemokines followed by the recruitment of leukocytes into the CNS. In this study, we analyzed the cellular and molecular mechanisms of polymorphonuclear neutrophil (PMN) and monocyte transepithelial transmigration (TM) across the BCSFB after bacterial infection. Methods Using an inverted transwell filter system of human choroid plexus papilloma cells (HIBCPP), we studied leukocyte TM rates, the migration route by immunofluorescence, transmission electron microscopy and focused ion beam/scanning electron microscopy, the secretion of cytokines/chemokines by cytokine bead array and posttranslational modification of the signal regulatory protein (SIRP) ? via western blot. Results PMNs showed a significantly increased TM across HIBCPP after infection with wild-type Neisseria meningitidis (MC58). In contrast, a significantly decreased monocyte transmigration rate after bacterial infection of HIBCPP could be observed. Interestingly, in co-culture experiments with PMNs and monocytes, TM of monocytes was significantly enhanced. Analysis of paracellular permeability and transepithelial electrical resistance confirmed an intact barrier function during leukocyte TM. With the help of the different imaging techniques we could provide evidence for para- as well as for transcellular migrating leukocytes. Further analysis of secreted cytokines/chemokines showed a distinct pattern after stimulation and transmigration of PMNs and monocytes. Moreover, the transmembrane glycoprotein SIRP? was deglycosylated in monocytes, but not in PMNs, after bacterial infection. Conclusions Our findings demonstrate that PMNs and monoctyes differentially migrate in a human BCSFB model after bacterial infection. Cytokines and chemokines as well as transmembrane proteins such as SIRP? may be involved in this process. PMID:23448224

  10. Fulminant Meningitis after Radiotherapy for Clival Chordoma

    PubMed Central

    Park, Hyun Wook; Park, Moon Sun; Chung, Seung Young; Park, Ki Seok; Lee, Do Sung; Oh, Jung Tae

    2013-01-01

    The best treatment for clival chordoma is obtained with total surgical excision, sometimes combined with adjuvant radiotherapy. A cerebrospinal fluid (CSF) fistula is a fatal complication that may occur following extended transsphenoidal surgery (TSS) and adjuvant radiotherapy. We report a case of fulminant meningitis without a CSF fistula in a 57-year-old woman who underwent TSS and multiple radiotherapies for a clival chordoma. She presented to our emergency room with copious epistaxis and odor inside her nasal cavity and had an unexpected fatal outcome. She was diagnosed with meningitis based on CSF culture and blood culture. While treating clival chordomas with adjuvant radiotherapy, clinicians should be aware of the possibility of fulminant meningitis. PMID:24904902

  11. Cerebrospinal fluid biomarker supported diagnosis of Creutzfeldt–Jakob disease and rapid dementias: a longitudinal multicentre study over 10 years

    PubMed Central

    Sanchez-Juan, Pascual; Gawinecka, Joanna; Green, Alison; Ladogana, Anna; Pocchiari, Maurizio; Sanchez-Valle, Raquel; Mitrova, Eva; Sklaviadis, Theodor; Kulczycki, Jerzy; Slivarichova, Dana; Saiz, Albert; Calero, Miguel; Knight, Richard; Aguzzi, Adriano; Laplanche, Jean-Louis; Peoc’h, Katell; Schelzke, Gabi; Karch, Andre; van Duijn, Cornelia M.; Zerr, Inga

    2012-01-01

    To date, cerebrospinal fluid analysis, particularly protein 14-3-3 testing, presents an important approach in the identification of Creutzfeldt–Jakob disease cases. However, one special point of criticism of 14-3-3 testing is the specificity in the differential diagnosis of rapid dementia. The constant observation of increased cerebrospinal fluid referrals in the national surveillance centres over the last years raises the concern of declining specificity due to higher number of cerebrospinal fluid tests performed in various neurological conditions. Within the framework of a European Community supported longitudinal multicentre study (‘cerebrospinal fluid markers’) we analysed the spectrum of rapid progressive dementia diagnoses, their potential influence on 14-3-3 specificity as well as results of other dementia markers (tau, phosphorylated tau and amyloid-?1–42) and evaluated the specificity of 14-3-3 in Creutzfeldt–Jakob disease diagnosis for the years 1998–2008. A total of 29 022 cerebrospinal fluid samples were analysed for 14-3-3 protein and other cerebrospinal fluid dementia markers in patients with rapid dementia and suspected Creutzfeldt–Jakob disease in the participating centres. In 10 731 patients a definite diagnosis could be obtained. Protein 14-3-3 specificity was analysed for Creutzfeldt–Jakob disease with respect to increasing cerebrospinal fluid tests per year and spectrum of differential diagnosis. Ring trials were performed to ensure the comparability between centres during the reported time period. Protein 14-3-3 test specificity remained high and stable in the diagnosis of Creutzfeldt–Jakob disease during the observed time period across centres (total specificity 92%; when compared with patients with definite diagnoses only: specificity 90%). However, test specificity varied with respect to differential diagnosis. A high 14-3-3 specificity was obtained in differentiation to other neurodegenerative diseases (95–97%) and non-neurological conditions (91–97%). We observed lower specificity in the differential diagnoses of acute neurological diseases (82–87%). A marked and constant increase in cerebrospinal fluid test referrals per year in all centres did not influence 14-3-3 test specificity and no change in spectrum of differential diagnosis was observed. Cerebrospinal fluid protein 14-3-3 detection remains an important test in the diagnosis of Creutzfeldt–Jakob disease. Due to a loss in specificity in acute neurological events, the interpretation of positive 14-3-3 results needs to be performed in the clinical context. The spectrum of differential diagnosis of rapid progressive dementia varied from neurodegenerative dementias to dementia due to acute neurological conditions such as inflammatory diseases and non-neurological origin. PMID:23012332

  12. Cerebrospinal fluid biomarker supported diagnosis of Creutzfeldt-Jakob disease and rapid dementias: a longitudinal multicentre study over 10 years.

    PubMed

    Stoeck, Katharina; Sanchez-Juan, Pascual; Gawinecka, Joanna; Green, Alison; Ladogana, Anna; Pocchiari, Maurizio; Sanchez-Valle, Raquel; Mitrova, Eva; Sklaviadis, Theodor; Kulczycki, Jerzy; Slivarichova, Dana; Saiz, Albert; Calero, Miguel; Knight, Richard; Aguzzi, Adriano; Laplanche, Jean-Louis; Peoc'h, Katell; Schelzke, Gabi; Karch, Andre; van Duijn, Cornelia M; Zerr, Inga

    2012-10-01

    To date, cerebrospinal fluid analysis, particularly protein 14-3-3 testing, presents an important approach in the identification of Creutzfeldt-Jakob disease cases. However, one special point of criticism of 14-3-3 testing is the specificity in the differential diagnosis of rapid dementia. The constant observation of increased cerebrospinal fluid referrals in the national surveillance centres over the last years raises the concern of declining specificity due to higher number of cerebrospinal fluid tests performed in various neurological conditions. Within the framework of a European Community supported longitudinal multicentre study ('cerebrospinal fluid markers') we analysed the spectrum of rapid progressive dementia diagnoses, their potential influence on 14-3-3 specificity as well as results of other dementia markers (tau, phosphorylated tau and amyloid-?(1-42)) and evaluated the specificity of 14-3-3 in Creutzfeldt-Jakob disease diagnosis for the years 1998-2008. A total of 29 022 cerebrospinal fluid samples were analysed for 14-3-3 protein and other cerebrospinal fluid dementia markers in patients with rapid dementia and suspected Creutzfeldt-Jakob disease in the participating centres. In 10 731 patients a definite diagnosis could be obtained. Protein 14-3-3 specificity was analysed for Creutzfeldt-Jakob disease with respect to increasing cerebrospinal fluid tests per year and spectrum of differential diagnosis. Ring trials were performed to ensure the comparability between centres during the reported time period. Protein 14-3-3 test specificity remained high and stable in the diagnosis of Creutzfeldt-Jakob disease during the observed time period across centres (total specificity 92%; when compared with patients with definite diagnoses only: specificity 90%). However, test specificity varied with respect to differential diagnosis. A high 14-3-3 specificity was obtained in differentiation to other neurodegenerative diseases (95-97%) and non-neurological conditions (91-97%). We observed lower specificity in the differential diagnoses of acute neurological diseases (82-87%). A marked and constant increase in cerebrospinal fluid test referrals per year in all centres did not influence 14-3-3 test specificity and no change in spectrum of differential diagnosis was observed. Cerebrospinal fluid protein 14-3-3 detection remains an important test in the diagnosis of Creutzfeldt-Jakob disease. Due to a loss in specificity in acute neurological events, the interpretation of positive 14-3-3 results needs to be performed in the clinical context. The spectrum of differential diagnosis of rapid progressive dementia varied from neurodegenerative dementias to dementia due to acute neurological conditions such as inflammatory diseases and non-neurological origin. PMID:23012332

  13. Altered Concentrations of Amyloid Precursor Protein Metabolites in the Cerebrospinal Fluid of Patients with Bipolar Disorder

    PubMed Central

    Jakobsson, Joel; Zetterberg, Henrik; Blennow, Kaj; Johan Ekman, Carl; Johansson, Anette G M; Landén, Mikael

    2013-01-01

    Bipolar disorder is a psychiatric disorder characterized by recurrent episodes of mania/hypomania and depression. Progressive cognitive dysfunction such as impairments in executive function and verbal memory is common in euthymic bipolar patients. The cerebrospinal fluid has previously been used to study neurodegenerative processes in Alzheimer's disease, from which changes in three core biomarkers have emerged as indicative of degeneration: amyloid ?, total tau, and hyperphosphorylated tau. Here, neurodegeneration in bipolar disorder was investigated by assessing the association between bipolar disorder and cerebrospinal fluid biomarkers for neurodegenerative processes. Cerebrospinal fluid was obtained from 139 bipolar disorder patients and 71 healthy controls. Concentrations of total and phosphorylated tau, amyloid ?1-42, amyloid ?38/?40/?42, and the soluble forms of amyloid precursor protein were measured in patients vs controls. The concentrations of the soluble forms of amyloid precursor protein were significantly lower in bipolar patients compared with controls. The amyloid ?42/amyloid ?38 and the amyloid ?42/amyloid ?40 ratios were higher in bipolar patients than controls. There were no discernible differences in the concentrations of total/phosphorylated tau, amyloid ?1-42, or amyloid ?38/?40/?42. The concentrations of the biomarkers within the bipolar patient group were further associated with different ongoing medical treatments and diagnostic subgroups. The findings suggest that the amyloid precursor protein metabolism is altered in bipolar disorder. The results may have implications for the understanding of the pathophysiology of bipolar disorder and for the development of treatment strategies. Importantly, there were no signs of an Alzheimer-like neurodegenerative process among bipolar patients. PMID:23212456

  14. The Risk of Meningitis Following Expanded Endoscopic Endonasal Skull Base Surgery: A Systematic Review

    PubMed Central

    Lai, Leon T.; Trooboff, Spencer; Morgan, Michael K.; Harvey, Richard J.

    2013-01-01

    Objective?To examine the risk of postoperative meningitis following expanded endoscopic endonasal skull base (EESB) surgery. Setting?A systematic analysis of publications identified through searches of the electronic databases from Embase (1980–July 17, 2012), Medline (1950–July 17, 2012), and references of review articles. Main Outcome Measures?Incidence of meningitis following EESB surgery. Results?A total of 2,444 manuscripts were selected initially, and full-text analysis produced 67 studies with extractable data. Fifty-two contained data regarding the frequency of postoperative meningitis. The overall risk of postoperative meningitis following EESB surgery was 1.8% (36 of 2,005). For those reporting a cerebrospinal fluid (CSF) leak, meningitis occurred in 13.0% (35 of 269). For those not reporting a CSF leak, meningitis occurred in 0.1% (1 of 1,736). The odds ratio for the development of meningitis in the presence of a postoperative CSF leak was 91.99 (95% confidence interval, 11.72–721.88; p?meningitis or CSF leak between anterior and posterior cranial fossa surgery. There was one reported case of meningitis-related mortality following EESB surgery. Conclusion?The evidence in skull base surgery is limited. This study demonstrates a low incidence of meningitis (1.8%) following EESB procedures. The incidence of meningitis from EESB surgery without an associated CSF leak is uncommon. PMID:24498585

  15. Transclival cerebrospinal fluid rhinorrhea as the initial presenting symptom of a tiny intradural chordoma.

    PubMed

    Feng, Kong; Qiuhang, Zhang; Qiuyi, Qu

    2010-08-01

    We report a patient with a tiny intradural clival chordoma, which was identified following presentation with cerebrospinal fluid (CSF) rhinorrhea as the initial symptom. The transclival dural defect and the intradural tumor were successfully localized by both radiological investigation and intraoperative endoscopic inspection. The tumor was totally resected and the CSF fistula was repaired by an endoscopic endonasal approach. The diagnosis, possible mechanisms and management of this rare condition are discussed. The role of endoscopy in identifying and treating the clival CSF rhinorrhea is emphasized. To our knowledge, this is the first report of a clival fistula secondary to a tiny intradural chordoma. PMID:20554205

  16. Definitive diagnosis of cerebrospinal fluid leak into the pleural space using 111In-DTPA cisternography.

    PubMed

    Howard, Brandon A; Gray, Linda; Isaacs, Robert E; Borges-Neto, Salvador

    2015-03-01

    A 58-year-old woman with a calcified disk extrusion causing severe spinal stenosis underwent T8 to T9 diskectomy and spinal fusion. A postoperative pseudomeningocele was treated with lumbar drain and fibrin glue. Performed for persistent right pleural effusion, CT myelogram failed to show communication between the cerebrospinal fluid (CSF) and pleural space--even on 2-hour delayed images. Subsequent 111In-DTPA cisternogram clearly demonstrated CSF leakage into the right pleural space at 2 hours, and surgical repair yielded good results. Radionuclide cisternography is a highly useful method to detect CSF leak, especially when it is occult on CT yet suspected clinically. PMID:25243944

  17. Elevated levels of phosphorylated neurofilament proteins in cerebrospinal fluid of Alzheimer disease patients

    Microsoft Academic Search

    Yuan-Yuan Hu; Shan-Shu He; Xiao-Chuang Wang; Qiu-Hong Duan; Sabiha Khatoon; Khalid Iqbal; Inge Grundke-Iqbal; Jian-Zhi Wang

    2002-01-01

    Neurofilament (NF) subunits NF-H, NF-M and NF-L are hyperphosphorylated and elevated in Alzheimer disease (AD) brain. We investigated the level and phosphorylation states of NF subunits in lumbar cerebrospinal fluid (CSF) from living patients by bienzyme substrate-recycle enzyme-linked immunosorbent assay. We found: (i), that the levels of phosphorylated NF-H\\/M (pNF-H\\/M), non-phosphorylated NF-H\\/M (npNF-H\\/M) and NF-L were significantly higher (pNF-H\\/M, ?12–24-fold;

  18. Lumbar cerebrospinal fluid concentrations of somatostatin and neuropeptide Y in multiple sclerosis

    SciTech Connect

    Vecsei, L.; Csala, B.; Widerloev, E.E.; Ekman, R.; Czopf, J.; Palffy, G. (Univ. of Lund (Sweden))

    1990-09-01

    The cerebrospinal fluid (CSF) concentrations of somatostatin and neuropeptide Y were investigated by use of radioimmunoassay in patients suffering from chronic progressive multiple sclerosis. The somatostatin level was significantly decreased in the CSF of patients with multiple sclerosis compared to the control group. The magnitude of this change was more pronounced in patients with severe clinical symptoms of the illness. The CSF neuropeptide Y concentration did not differ from the control values. These findings suggest a selective involvement of somatostatin neurotransmission in multiple sclerosis.

  19. Decreased concentration of Klotho in the cerebrospinal fluid of patients with relapsing-remitting multiple sclerosis.

    PubMed

    Emami Aleagha, Mohammad Sajad; Siroos, Bahaadin; Ahmadi, Mona; Balood, Mohammad; Palangi, Alireza; Haghighi, Afsaneh Nazari; Harirchian, Mohammad Hossein

    2015-04-15

    Recent investigations support that an anti-aging protein, namely Klotho, protects neurons against the oxidative stress and demyelination. We evaluated the protein concentration of Klotho and total anti-oxidant capacity (TAC) in the cerebrospinal fluid (CSF) of patients with relapsing-remitting multiple sclerosis (RRMS). Klotho concentration and TAC were significantly lower in patients as compared to controls. Klotho values showed a significant negative correlation with expanded disability status scale (EDSS). Moreover, a significantly positive correlation between TAC levels and Klotho concentrations was detected. Klotho may play an important role in the pathogenesis of MS, at least in part, through the regulation of redox system. PMID:25867461

  20. Digital PCR technology detects brain-tumor-associated mutation in cerebrospinal fluid

    Cancer.gov

    Researchers from the Massachusetts General Hospital (a component of the Dana-Farber Cancer Institute) and their colleagues have used digital versions of a standard molecular biology tool to detect a common tumor-associated mutation in the cerebrospinal fluid (CSF) of patients with brain tumors. In their report being published in the open-access journal Molecular Therapy – Nucleic Acids, the investigators describe using advanced forms of the gene-amplification technology polymerase chain reaction (PCR) to analyze bits of RNA carried in membrane-covered sacs called extracellular vesicles for the presence of a tumor-associated mutation in a gene called IDH1.

  1. Total glutamine synthetase levels in cerebrospinal fluid of Alzheimer's disease patients are unchanged.

    PubMed

    Timmer, Nienke M; Herbert, Megan K; Claassen, Jurgen A H R; Kuiperij, H Bea; Verbeek, Marcel M

    2015-03-01

    Decreased cerebral protein and activity levels of glutamine synthetase (GS) have been reported for Alzheimer's disease (AD) patients. Using a recently established method, we quantified total GS levels in cerebrospinal fluid (CSF) from AD patients and control subjects. Furthermore, we investigated if total GS levels in CSF could differentiate AD from frontotemperal dementia and dementia with Lewy bodies patients. As we found no significantly altered total GS levels in any of the patient groups compared with control subjects, we conclude that levels of total GS in CSF have no diagnostic value for AD, dementia with Lewy bodies, or frontotemperal dementia. PMID:25577411

  2. Computational investigation of subject-specific cerebrospinal fluid flow in the third ventricle and aqueduct of Sylvius

    Microsoft Academic Search

    Vartan Kurtcuoglu; Michaela Soellinger; Paul Summers; Kevin Boomsma; Dimos Poulikakos; Peter Boesiger; Yiannis Ventikos

    2007-01-01

    The cerebrospinal fluid flow in the third ventricle of the brain and the aqueduct of Sylvius was studied using computational fluid dynamics (CFD) based on subject-specific boundary conditions derived from magnetic resonance imaging (MRI) scans. The flow domain geometry was reconstructed from anatomical MRI scans by manual image segmentation. The movement of the domain boundary was derived from MRI brain

  3. Alzheimer’s disease: roles for mitochondrial damage, the hydroxyl radical, and cerebrospinal fluid deficiency of melatonin

    Microsoft Academic Search

    C. P. Maurizi

    2001-01-01

    A deficiency of cerebrospinal fluid melatonin is postulated to be critical for the development of Alzheimer’s disease. Some melatonin is normally secreted directly into the fluid inducing higher levels than in simultaneously sampled blood. Melatonin is carried into the ventricular system via choroid plexus portals. The neurohormone is a potent antioxidant that passes through cell membranes with ease and is

  4. Varicella zoster virus meningitis with hypoglycorrhachia in the absence of rash in an immunocompetent woman

    PubMed Central

    Habib, Ali A; Gilden, Don; Schmid, D Scott; Safdieh, Joseph E

    2009-01-01

    We report varicella-zoster virus (VZV) meningitis in a healthy adult woman with no antecedent rash and with hypoglycorrhachia. Cerebrospinal fluid (CSF) examination revealed the presence of VZV DNA, anti-VZV immunoglobulin G (IgG) antibody, and intrathecal production of anti-VZV IgG antibody. PMID:19255900

  5. Varicella zoster virus meningitis with hypoglycorrhachia in the absence of rash in an immunocompetent woman

    Microsoft Academic Search

    Ali A. Habib; Don Gilden; D. Scott Schmid; Joseph E. Safdieh

    2009-01-01

    We report varicella-zoster virus (VZV) meningitis in a healthy adult woman with no antecedent rash and with hypoglycorrhachia.\\u000a Cerebrospinal fluid (CSF) examination revealed the presence of VZV DNA, anti-VZV immunoglobulin G (IgG) antibody, and intrathecal\\u000a production of anti-VZV IgG antibody.

  6. Microsatellite typing and susceptibilities of serial Cryptococcus neoformans isolates from Cuban patients with recurrent cryptococcal meningitis

    Microsoft Academic Search

    María T Illnait-Zaragozí; Gerardo F Martínez-Machín; Carlos M Fernández-Andreu; Ferry Hagen; Teun Boekhout; Corné HW Klaassen; Jacques F Meis

    2010-01-01

    BACKGROUND: Cryptococcus neoformans is commonly associated with meningoencephalitis in immunocompromised patients and occasionally in apparently healthy individuals. Recurrence of infection after initial treatment is not uncommon. We studied C. neoformans isolates from 7 Cuban patients with recurrent cryptococcal meningitis. Antifungal susceptibility and genotyping with microsatellite molecular typing were carried out. METHODS: Isolates (n = 19) were recovered from cerebrospinal fluid,

  7. Aseptic Meningitis and Encephalitis: the Role of PCR in the Diagnostic Laboratory

    Microsoft Academic Search

    STEVEN J. READ; KATIE J. M. JEFFERY; ANDCHARLES R. M. BANGHAM

    In this study we have devised a simple and robust PCR strategy to detect a wide range of viruses, bacteria, and parasites, all of which are capable of causing aseptic meningitis and encephalitis. The techniques developed have been used in a routine diagnostic virology laboratory to test prospectively 2,233 cerebrospinal fluid specimens. A virus was detected in 147 specimens of

  8. Eosinophilic meningitis: a case series and review of literature of Angiostrongylus cantonensis and Gnathostoma spinigerum.

    PubMed

    Shah, I; Barot, S; Madvariya, M

    2015-01-01

    Eosinophilic meningitis is defined as the presence of >10 eosinophils/?L in cerebrospinal fluid (CSF) or at least 10% eosinophils in the total CSF leukocyte count. Eosinophilic meningitis has been reported in two case series and two case reports in India till date and has not been reported in children below 15 years of age. We present two children with eosinophilic meningitis with peripheral eosinophilia and the proposed etiologic agents based on the clinical setting and their response to antihelminthic agents. PMID:25560024

  9. Cerebrospinal Fluid ?-Synuclein Predicts Cognitive Decline in Parkinson Disease Progression in the DATATOP Cohort

    PubMed Central

    Stewart, Tessandra; Liu, Changqin; Ginghina, Carmen; Cain, Kevin C.; Auinger, Peggy; Cholerton, Brenna; Shi, Min; Zhang, Jing

    2015-01-01

    Most patients with Parkinson disease (PD) develop both cognitive and motor impairment, and biomarkers for progression are urgently needed. Although ?-synuclein is altered in cerebrospinal fluid of patients with PD, it is not known whether it predicts motor or cognitive deterioration. We examined clinical data and ?-synuclein in >300 unmedicated patients with PD who participated in the deprenyl and tocopherol antioxidative therapy of parkinsonism (DATATOP) study, with up to 8 years of follow-up. Longitudinal measures of motor and cognitive function were studied before (phase 1) and during (phase 2) levodopa therapy; cerebrospinal fluid was collected at the beginning of each phase. Correlations and linear mixed models were used to assess ?-synuclein association with disease severity and prediction of progression in the subsequent follow-up period. Despite decreasing ?-synuclein (phase 1 to phase 2 change of ?0.05 ± 0.21 log-transformed values, P < 0.001), no correlations were observed between ?-synuclein and motor symptoms. Longitudinally, lower ?-synuclein predicted better preservation of cognitive function by several measures [Selective Reminding Test total recall ?-synuclein × time interaction effect coefficient, ?0.12 (P = 0.037); delayed recall, ?0.05 (P = 0.002); New Dot Test, ?0.03 (P = 0.002)]. Thus, ?-synuclein, although not clinically useful for motor progression, might predict cognitive decline, and future longitudinal studies should include this outcome for further validation. PMID:24625392

  10. Blood-Cerebrospinal Fluid Barrier Permeability in Alzheimer’s Disease1

    PubMed Central

    Chalbot, Sonia; Zetterberg, Henrik; Blennow, Kaj; Fladby, Tormod; Andreasen, Niels; Grundke-Iqbal, Inge; Iqbal, Khalid

    2011-01-01

    The role of blood-cerebrospinal fluid barrier (BCB) dysfunction in Alzheimer’s disease (AD) has been addressed but not yet established. We evaluated the BCB integrity in 179 samples of cerebrospinal fluid (CSF) retrospectively collected from AD patients and control cases using both CSF/serum albumin ratio (QAlb) and CSF secretory Ca2+-dependent phospholipase A2 (sPLA2) activity. These analyses were supplemented with the measurement of total tau, amyloid-?1–42 (A?1–42), and ubiquitin CSF levels. We found that due to its higher sensitivity, CSF sPLA2 activity could 1) discriminate AD from healthy controls and 2) showed BCB impairment in neurological control cases while QAlb could not. Moreover, the CSF sPLA2 activity measurement showed that around half of the AD patients were characterized by a BCB impairment. The BCB dysfunction observed in AD was independent from Mini-Mental State Examination score as well as CSF levels of total tau, A?1–42, and ubiquitin. Finally, the BCB dysfunction was not limited to any of the CSF biomarkers-based previously identified subgroups of AD. These results suggest that the BCB damage occurs independent of and probably precedes both A? and tau pathologies in a restricted subgroup of AD patients. PMID:21471645

  11. In vivo phage display screen for peptide sequences that cross the blood-cerebrospinal-fluid barrier.

    PubMed

    Li, Jingwei; Feng, Liang; Jiang, Xinguo

    2015-02-01

    There is lack of a barrier between CSF and brain, thus peptide that can cross the blood-cerebrospinal-fluid barrier (BCSFB) will have a greater chance of providing access to the brain. In this study, we screened for a novel peptide sequence that can cross the BCSFB from the systemic circulation using phage display. We applied a 12-mer phage display peptide library (Ph.D.-12) intravenously in rats and recovered phage from the cerebrospinal fluid. A longer circulation time was used according to the biodistributive CSF/blood ratio of the phage particles. Following sequential rounds of isolation, several phages were sequenced, and a peptide sequence (TPSYDTYAAELR, referred to as the TPS peptide) was identified. Clone 12-1, which encoded the TPS peptide, was enriched approximately 53 times greater than the random library phage. After labeling with FITC, the TPS peptide demonstrated significantly greater brain accumulation efficiency. This study demonstrates the feasibility of using in vivo phage display to screen for peptides that can cross the BCSFB from the systemic circulation. In conclusion, the TPS peptide represents a previously unreported promising motif that can be used to design a drug delivery system that can cross the BCSFB. PMID:25408466

  12. GWAS of cerebrospinal fluid tau levels identifies risk variants for Alzheimer's disease.

    PubMed

    Cruchaga, Carlos; Kauwe, John S K; Harari, Oscar; Jin, Sheng Chih; Cai, Yefei; Karch, Celeste M; Benitez, Bruno A; Jeng, Amanda T; Skorupa, Tara; Carrell, David; Bertelsen, Sarah; Bailey, Matthew; McKean, David; Shulman, Joshua M; De Jager, Philip L; Chibnik, Lori; Bennett, David A; Arnold, Steve E; Harold, Denise; Sims, Rebecca; Gerrish, Amy; Williams, Julie; Van Deerlin, Vivianna M; Lee, Virginia M-Y; Shaw, Leslie M; Trojanowski, John Q; Haines, Jonathan L; Mayeux, Richard; Pericak-Vance, Margaret A; Farrer, Lindsay A; Schellenberg, Gerard D; Peskind, Elaine R; Galasko, Douglas; Fagan, Anne M; Holtzman, David M; Morris, John C; Goate, Alison M

    2013-04-24

    Cerebrospinal fluid (CSF) tau, tau phosphorylated at threonine 181 (ptau), and A??? are established biomarkers for Alzheimer's disease (AD) and have been used as quantitative traits for genetic analyses. We performed the largest genome-wide association study for cerebrospinal fluid (CSF) tau/ptau levels published to date (n = 1,269), identifying three genome-wide significant loci for CSF tau and ptau: rs9877502 (p = 4.89 × 10?? for tau) located at 3q28 between GEMC1 and OSTN, rs514716 (p = 1.07 × 10?? and p = 3.22 × 10?? for tau and ptau, respectively), located at 9p24.2 within GLIS3 and rs6922617 (p = 3.58 × 10?? for CSF ptau) at 6p21.1 within the TREM gene cluster, a region recently reported to harbor rare variants that increase AD risk. In independent data sets, rs9877502 showed a strong association with risk for AD, tangle pathology, and global cognitive decline (p = 2.67 × 10??, 0.039, 4.86 × 10??, respectively) illustrating how this endophenotype-based approach can be used to identify new AD risk loci. PMID:23562540

  13. Evaluation of three tracers for labeling distal cerebrospinal fluid-contacting neurons.

    PubMed

    Zhou, Fang; Wang, Jiayou; Zhang, Hongxing; Liu, He; Zhao, Guangping; Zu, Cuihua; Lu, Xiaoxing; Zhang, Licai

    2013-10-01

    It has been reported that distal cerebrospinal fluid-contacting neurons (dCSF-CNs) can be detected by immunohistochemical assay using cholera toxin subunit B-conjugated horseradish peroxidase (CB-HRP). In the present study, another two methods with CB alone or CB-conjugated FITC (CB-FITC) were used, and the results from the three methods were compared. Adult Sprague-Dawley rats were randomly divided into three groups with CB-HRP, CB or CB-FITC. Tracers were diluted to 30% in artificial cerebrospinal fluid and injected separately (in a volume of 3 ?L) into the lateral ventricle. Animals from the CB-HRP and CB groups were perfused 48 h after surgery while animals from the CB-FITC group were perfused 1, 3, 6, 12, 24 or 48 h after surgery. The brain was sectioned (40 ?m) for immunofluorescence and five sections with positive neurons were selected from each rat for neuron counting. Three clusters of positive neurons in a 'Y-like' distribution were detected ventral to the cerebral aqueduct of rats from the three groups. No significant difference was observed among the quantitative data. In the CB-FITC group, stable staining was detected even at 6 h after injection. Taken together, lateral ventricle injection of CB/CB-FITC is a useful method for labeling dCSF-CNs in rats. The CB-FITC method makes dCSF-CNs labeling much simpler and more convenient. PMID:23585297

  14. Cerebrospinal fluid ?-synuclein predicts cognitive decline in Parkinson disease progression in the DATATOP cohort.

    PubMed

    Stewart, Tessandra; Liu, Changqin; Ginghina, Carmen; Cain, Kevin C; Auinger, Peggy; Cholerton, Brenna; Shi, Min; Zhang, Jing

    2014-04-01

    Most patients with Parkinson disease (PD) develop both cognitive and motor impairment, and biomarkers for progression are urgently needed. Although ?-synuclein is altered in cerebrospinal fluid of patients with PD, it is not known whether it predicts motor or cognitive deterioration. We examined clinical data and ?-synuclein in >300 unmedicated patients with PD who participated in the deprenyl and tocopherol antioxidative therapy of parkinsonism (DATATOP) study, with up to 8 years of follow-up. Longitudinal measures of motor and cognitive function were studied before (phase 1) and during (phase 2) levodopa therapy; cerebrospinal fluid was collected at the beginning of each phase. Correlations and linear mixed models were used to assess ?-synuclein association with disease severity and prediction of progression in the subsequent follow-up period. Despite decreasing ?-synuclein (phase 1 to phase 2 change of -0.05 ± 0.21 log-transformed values, P < 0.001), no correlations were observed between ?-synuclein and motor symptoms. Longitudinally, lower ?-synuclein predicted better preservation of cognitive function by several measures [Selective Reminding Test total recall ?-synuclein × time interaction effect coefficient, -0.12 (P = 0.037); delayed recall, -0.05 (P = 0.002); New Dot Test, -0.03 (P = 0.002)]. Thus, ?-synuclein, although not clinically useful for motor progression, might predict cognitive decline, and future longitudinal studies should include this outcome for further validation. PMID:24625392

  15. The Th1 versus Th2 cytokine profile in cerebrospinal fluid after severe traumatic brain injury in infants and children.

    PubMed

    Amick, Jonathan E.; Yandora, Kristin A.; Bell, Michael J.; Wisniewski, Stephen R.; Adelson, P. David; Carcillo, Joseph A.; Janesko, Keri L.; DeKosky, Steven T.; Carlos, Timothy M.; Clark, Robert S.B.; Kochanek, Patrick M.

    2001-07-01

    OBJECTIVE: To further characterize the Th1 (proinflammatory) vs. the Th2 (antiinflammatory) cytokine profile after severe traumatic brain injury (TBI) by quantifying the ventricular cerebrospinal fluid concentrations of Th1 cytokines (interleukin [IL]-2 and IL-12) and Th2 cytokines (IL-6 and IL-12) in infants and children. DESIGN: Retrospective study. SETTING: University children's hospital. PATIENTS: Twenty-four children hospitalized with severe TBI (admission Glasgow Coma Scale score, <13) and 12 controls with negative diagnostic lumbar punctures. INTERVENTIONS: All TBI patients received standard neurointensive care, including the placement of an intraventricular catheter for continuous drainage of cerebrospinal fluid. MEASUREMENTS AND MAIN RESULTS: Ventricular cerebrospinal fluid samples (n = 105) were collected for as long as the catheters were in place (between 4 hrs and 222 hrs after TBI). Cerebrospinal fluid samples were analyzed for IL-2, IL-4, IL-6, and IL-12 concentrations by enzyme-linked immunoassay. Peak and mean IL-6 (335.7 +/- 41.4 pg/mL and 259.5 +/- 37.6 pg/mL, respectively) and IL-12 (11.4 +/- 2.2 pg/mL and 4.3 +/- 0.8 pg/mL, respectively) concentrations were increased (p <.05) in children after TBI vs. controls (2.3 +/- 0.7 pg/mL and 1.0 +/- 0.5 pg/mL) for IL-6 and IL-12, respectively. In contrast, peak and mean IL-2 and IL-4 concentrations were not increased in TBI children vs. controls. Increases in the cerebrospinal fluid concentration of IL-6 were significantly associated with admission Glasgow Coma Scale score of cerebrospinal fluid IL-4 and IL-12 were associated with child abuse as an injury mechanism (both p cerebrospinal fluid after TBI in infants and children. It is the first report of increased IL-12 levels in cerebrospinal fluid after TBI in infants and children. Further, it is the first to report on IL-2 and IL-4 levels in pediatric or adult TBI. These data suggest that selected members of both the Th1 and Th2 cytokine families are increased as part of the endogenous inflammatory response to TBI. Finally, in that both IL-6 and IL-12 (but neither IL-2 nor IL-4) can be produced by astrocytes and/or neurons, a parenchymal source for cytokines in the brain after TBI may be critical to their production in the acute phase after TBI. PMID:12793952

  16. Gas Chromatography-Mass Spectrometry-Based Metabolic Profiling of Cerebrospinal Fluid from Epileptic Dogs

    PubMed Central

    HASEGAWA, Tetsuya; SUMITA, Maho; HORITANI, Yusuke; TAMAI, Reo; TANAKA, Katsuhiro; KOMORI, Masayuki; TAKENAKA, Shigeo

    2013-01-01

    ABSTRACT Epilepsy is a common neurological disorder with seizures, but diagnostic approaches in veterinary clinics remain limited. Cerebrospinal fluid (CSF) is a body fluid used for diagnosis in veterinary medicine. In this study, we explored canine epilepsy diagnostic biomarkers using gas chromatography-mass spectrometry (GC-MS)-based metabolic profiling of CSF and multivariate data analysis. Profiles for subjects with idiopathic epilepsy differed significantly from those of healthy controls and subjects with symptomatic epilepsy. Among 60 identified metabolites, the levels of 20 differed significantly among the three groups. Glutamic acid was significantly increased in idiopathic epilepsy, and some metabolites including ascorbic acid were changed in both forms of epilepsy. These findings show that metabolic profiles of CSF differ between idiopathic and symptomatic epilepsy and that metabolites including glutamic acid and ascorbic acid in CSF may be useful for diagnosis of canine epilepsy. PMID:24334864

  17. Alzheimer's disease: roles for mitochondrial damage, the hydroxyl radical, and cerebrospinal fluid deficiency of melatonin.

    PubMed

    Maurizi, C P

    2001-08-01

    A deficiency of cerebrospinal fluid melatonin is postulated to be critical for the development of Alzheimer's disease. Some melatonin is normally secreted directly into the fluid inducing higher levels than in simultaneously sampled blood. Melatonin is carried into the ventricular system via choroid plexus portals. The neurohormone is a potent antioxidant that passes through cell membranes with ease and is concentrated in mitochondria. Neural tissue in contact with the ventricular system will have high levels of cellular melatonin. In Alzheimer's disease, inadequate melatonin allows hydroxyl radicals produced by mitochondrial complex IV to damage mitochondria and initiate a cascade of oxygen radicals that causes the neuropathological changes in Alzheimer's disease. Results from initial therapeutic trials of melatonin in Alzheimer's disease patients have demonstrated improved function, decreased 'sundowning', improved sleep, and a significant slowing of the progression of the disease. PMID:11461164

  18. Repeat lumbar puncture in the diagnosis of meningitis.

    PubMed Central

    Kindley, A D; Harris, F

    1978-01-01

    Meningitis may be difficult to diagnose. If it is suspected clinically and a first lumbar puncture is normal, a second cerebrospinal fluid (CSF) sample may be required within a few hours to confirm the diagnosis. A child is presented in whom CSF was normal 14 hours after the onset of illness, but who 14 hours later showed the characteristic changes of purulent meningitis. This case differs from those previously cited in the literature, in that the blood cultures taken at the time of the first lumbar puncture were also negative. PMID:686797

  19. False-positive latex agglutination test for Neisseria meningitidis groups A and Y caused by povidone-iodine antiseptic contamination of cerebrospinal fluid.

    PubMed Central

    D'Amato, R F; Hochstein, L; Fay, E A

    1990-01-01

    The cerebrospinal fluid of a patient yielded a positive latex agglutination test for Neisseria meningitidis groups A and Y. The latex agglutination results were not consistent with clinical and other laboratory findings. An investigation determined that the positive agglutination test was caused by contamination of the cerebrospinal fluid with povidone-iodine during the lumbar puncture. PMID:2121794

  20. Leukocyte Attraction by CCL20 and Its Receptor CCR6 in Humans and Mice with Pneumococcal Meningitis

    PubMed Central

    Angele, Barbara; Geldhoff, Madelijn; Marquez, Gabriel; Varona, Rosa; Häcker, Georg; Schmetzer, Helga; Häcker, Hans; Hammerschmidt, Sven; van der Ende, Arie; Pfister, Hans-Walter

    2014-01-01

    We previously identified CCL20 as an early chemokine in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis but its functional relevance was unknown. Here we studied the role of CCL20 and its receptor CCR6 in pneumococcal meningitis. In a prospective nationwide study, CCL20 levels were significantly elevated in the CSF of patients with pneumococcal meningitis and correlated with CSF leukocyte counts. CCR6-deficient mice with pneumococcal meningitis and WT mice with pneumococcal meningitis treated with anti-CCL20 antibodies both had reduced CSF white blood cell counts. The reduction in CSF pleocytosis was also accompanied by an increase in brain bacterial titers. Additional in vitro experiments showed direct chemoattractant activity of CCL20 for granulocytes. In summary, our results identify the CCL20-CCR6 axis as an essential component of the innate immune defense against pneumococcal meningitis, controlling granulocyte recruitment. PMID:24699535

  1. Varicella-zoster meningitis with a late-onset of skin eruption.

    PubMed

    Sanguankeo, Anawin; Upala, Sikarin; Sornprom, Suthanya; Thamcharoen, Natanong

    2015-01-01

    Viral meningitis caused by varicella-zoster virus (VZV) is an uncommon neurological complication of herpes zoster. It may occur before or after the onset of the vesicular rash along the dermatomal distribution, which is the classic presentation of herpes zoster. We describe a case of a 51-year-old immunocompetent Caucasian man who presented with neck and severe right-sided facial pain. Eight days later, he had photophobia and papular rash on his forehead. Cerebrospinal fluid (CSF) examination confirmed aseptic meningitis and CSF PCR detected the presence of VZV DNA. Neurological complications of VZV infection, such as aseptic meningitis, may be difficult to diagnose and can cause delay in treatment, especially in cases with late onset of dermatological manifestations of herpes zoster. Definite diagnosis requires evidence of acute VZV infection in blood or cerebrospinal fluid. PMID:25691578

  2. Detection of enterovirus RNA in cerebrospinal fluid (CSF) using NucliSens EasyQ Enterovirus assay.

    PubMed

    Capaul, S E; Gorgievski-Hrisoho, M

    2005-03-01

    Rapid detection of enterovirus (EV) infections is essential in the management of aseptic meningitis. Molecular approaches have opened the way to such rapid, but also specific and sensitive, diagnostic tests. The aim of this study was to compare the performance of the CE marked NucliSens EasyQ Enterovirus assay with an in-house two-step RT-PCR assay using cerebrospinal fluid (CSF) and throat swab samples. In addition, specificity was tested with clinical isolates positive for viruses with clinical importance in CSF samples. For nucleic acid extraction, the NucliSens miniMAG and NucliSens magnetic extraction reagents were used. Subsequently real-time nucleic acid sequence-based amplification (NASBA) RNA amplification was performed using NucliSens EasyQ basic kit reagents and NucliSens EasyQ Enterovirus reagents. An EV-specific internal homologous control (IC) RNA was used to monitor the entire NucliSens EasyQ procedure at the individual sample level. No IC but an external inhibition control was available for the RT-PCR method. For the NucliSens EasyQ procedure, amplification and real-time detection reactions were carried out in the NucliSens EasyQ analyzer. The real-time NASBA enterovirus detection was based on NASBA amplification and real-time molecular beacon technology. Data were analyzed using the manufacturer's software on the NucliSens EasyQ analyzer. For the in-house assay, RT-PCR amplicons were detected using agarose gel analysis. The analysis of clinical samples positive for HSV-1, HSV-2, adenovirus, CMV, VZV, mumps and rhinovirus were all negative by NucliSens EasyQ Enterovirus assay. Three rhinovirus samples were, however, strongly positive in RT-PCR. A total of 141 clinical samples were retrospectively tested, including 126 cerebrospinal fluid (CSF) samples and 15 throat swabs. The 91 CSF samples were negative by both methods, 31 CSF samples and 14 throat swab samples were positive by both methods. The four CSF samples were positive by RT-PCR only. One throat swab sample was negative in NucliSens EasyQ but positive in RT-PCR. The sensitivity and specificity of both methods seem to be more or less comparable. However, the in-house RT-PCR assay appears to amplify some rhinovirus strains and should therefore not be used for throat swab samples. NucliSens EasyQ Enterovirus assay gave more invalid results than the in-house RT-PCR, which is obvious taken into account the difference in quality control between the CE marked NucliSens EasyQ Enterovirus assay and the in-house enterovirus assay. The NucliSens EasyQ procedure can be completed within 5h versus 9.5h for the RT-PCR. NucliSens EasyQ Enterovirus assay showed to be a standardized, rapid, specific, sensitive and reliable procedure for the detection of enterovirus RNA. PMID:15722029

  3. Neural Differentiation of Human Umbilical Cord Mesenchymal Stem Cells by Cerebrospinal Fluid

    PubMed Central

    FARIVAR, Shirin; MOHAMADZADE, Zahra; SHIARI, Reza; FAHIMZAD, Alireza

    2015-01-01

    Objective Wharton’s jelly (WJ) is the gelatinous connective tissue from the umbilical cord. It is composed of mesenchymal stem cells, collagen fibers, and proteoglycans. The stem cells in WJ have properties that are interesting for research. For example, they are simple to harvest by noninvasive methods, provide large numbers of cells without risk to the donor, the stem cell population may be expanded in vitro, cryogenically stored, thawed, genetically manipulated, and differentiated in vitro. In our study, we investigated the effect of human cerebrospinal fluid (CSF) on neural differentiation of human WJ stem cells. Material & Methods The cells in passage 2 were induced into neural differentiation with different concentrations of human cerebrospinal fluid. Differentiation along with neural lineage was documented by expression of three neural markers: Nestin, Microtubule-Associated Protein 2 (MAP2), and Glial Fibrillary Astrocytic Protein (GFAP) for 21 days. The expression of the identified genes was confirmed by Reverse Transcriptase PCR (RT-PCR). Results Treatment with 100 and 200?g/ml CSF resulted in the expression of GFAP and glial cells marker on days 14 and 21. The expression of neural-specific genes following CSF treatment was dose-dependent and time-dependent. Treatment of the cells with a twofold concentration of CSF, led to the expression of MAP2 on day 14 of induction. No expression of GFAP was detected before day 14 or MAP2 before day 21, which shows the importance of the treatment period. In the present study, expression analysis for the known neural markers: Nestin, GFAP, and MAP2 using RT-PCR were performed. The data demonstrated that CSF could play a role as a strong inducer. Conclusion RT-PCR showed that cerebrospinal fluid promotes the expression of Nestin, MAP2, and GFAP mRNA in a dose-dependent manner, especially at a concentration of 200 ?l/ml. In summary, CSF induces neurogenesis of WJ stem cells that encourages tissue engineering applications with these cells for treatments of neurodegenerative defects and traumatic brain injury. PMID:25767544

  4. Determination of homovanillic acid, 5-hydroxyindoleacetic acid and pressure in the cerebrospinal fluid of Collie dogs following administration of ivermectin

    Microsoft Academic Search

    D. M. Vaughn; S. T. Simpson; B. L. Blagburn; W. L. Whitmer; R. Heddens-Mysinger; C. M. Hendrix

    1989-01-01

    Twelve adult Collie dogs were studied to determine the effects of ivermectin on neurotransmitter metabolites released from the brain into the cerebrospinal fluid (CSF) and on CSF pressure. Ten of the 12 Collies were given ivermectin orally at a concentration of 200 µg\\/kg body weight. Three of these 10 Collies showed clinical signs of ivermectin-induced toxicosis which progressed into a

  5. Quantification of tau phosphorylated at threonine 181 in human cerebrospinal fluid: a sandwich ELISA with a synthetic phosphopeptide for standardization

    Microsoft Academic Search

    E Vanmechelen; H Vanderstichele; P Davidsson; E Van Kerschaver; B Van Der Perre; M Sjögren; N Andreasen; K Blennow

    2000-01-01

    Hyperphosphorylation of the microtubule-associated protein tau is specifically found in those brain cells affected in several tauopathies. Tau has also been consistently found to be present in the cerebrospinal fluid (CSF). Here we report the quantification in CSF of tau phosphorylated at Thr 181 using an immunoassay with a synthetic peptide for standardization. The choice of the peptide was based

  6. Cerebrospinal fluid HIV-1 compartmentalization in a patient with AIDS and acute varicella-zoster virus meningomyeloradiculitis.

    PubMed

    Falcone, E Liana; Adegbulugbe, Ademiposi A; Sheikh, Virginia; Imamichi, Hiromi; Dewar, Robin L; Hammoud, Dima A; Sereti, Irini; Lane, H Clifford

    2013-09-01

    We report a case of AIDS presenting as varicella-zoster virus (VZV) meningomyeloradiculitis associated with human immunodeficiency virus (HIV) quasispecies compartmentalization within the cerebrospinal fluid (CSF), and a CSF viral load that was 1 log higher than in peripheral blood. Prolonged antiviral therapy for both VZV and HIV type 1 was associated with partial resolution. PMID:23728149

  7. Elevation of Gas6 protein concentration in cerebrospinal fluid of patients with chronic inflammatory demyelinating polyneuropathy (CIDP)

    Microsoft Academic Search

    Pier Paolo Sainaghi; Laura Collimedaglia; Federica Alciato; Maurizio A. Leone; Erinda Puta; Paola Naldi; Luigi Castello; Francesco Monaco; Gian Carlo Avanzi

    2008-01-01

    IntroductionGas6 enhances survival of Schwann cells and neurons in vitro and participates in autoimmunity in animal models. Since its concentration in human cerebrospinal fluid (CSF) is unknown, we measured it in samples from patients with non-inflammatory\\/non-autoimmune neurological diseases (NINAD) and autoimmune polyneuropathies.

  8. Cerebrospinal Fluid Corticotropin-Releasing Factor Concentration is Associated with Pain but not Fatigue Symptoms in Patients with Fibromyalgia

    Microsoft Academic Search

    Samuel A McLean; David A Williams; Phyllis K Stein; Richard E Harris; Angela K Lyden; Gail Whalen; Karen M Park; Israel Liberzon; Ananda Sen; Richard H Gracely; James N Baraniuk; Daniel J Clauw

    2006-01-01

    Previous studies have identified stress system dysregulation in fibromyalgia (FM) patients; such dysregulation may be involved in the generation and\\/or maintenance of pain and other symptoms. Corticotropin-releasing factor (CRF) is the principal known central nervous system mediator of the stress response; however, to date no studies have examined cerebrospinal fluid (CSF) CRF levels in patients with FM. The relationship between

  9. Antibodies in Cerebrospinal Fluid of Some Alzheimer Disease Patients Recognize Cholinergic Neurons in the Rat Central Nervous System

    Microsoft Academic Search

    Amanda McRae-Degueurce; Serney Booj; Kenneth Haglid; Lars Rosengren; Jan Erik Karlsson; Ingvar Karlsson; Anders Wallin; Lars Svennerholm; Carl-Gerhard Gottfries; Annica Dahlstrom

    1987-01-01

    The etiology of Alzheimer disease is unclear. However, immunological aberrations have been suggested to be critical factors in the pathogenesis of this neurodegenerative disease. This study was carried out to investigate if cerebrospinal fluid (CSF) from Alzheimer disease patients contains antibodies that recognize specific neuronal populations in the rat central nervous system. The results indicate that in a subgroup of

  10. Cerebrospinal Fluid Leptin in Anorexia Nervosa: Correlation with Nutritional Status and Potential Role in Resistance to Weight Gain

    Microsoft Academic Search

    CHRISTOS MANTZOROS; JEFFREY S. FLIER; MICHAEL D. LESEM; TIMOTHY D. BREWERTON; DAVID C. JIMERSON

    2010-01-01

    Studies in rodents have shown that leptin acts in the central ner- vous system to modulate food intake and energy metabolism. To evaluate the possible role of leptin in the weight loss of anorexia nervosa, this study compared cerebrospinal fluid (CSF) and plasma leptin concentrations in anorexic patients and controls. Subjects in- cluded 11 female patients with anorexia nervosa studied

  11. Increased prevalence of and gene transcription by Chlamydia pneumoniae in cerebrospinal fluid of patients with relapsing-remitting multiple sclerosis

    Microsoft Academic Search

    T. Dong-Si; J. Weber; Y. B. Liu; C. Buhmann; H. Bauer; C. Bendl; P. Schnitzler; C. Grond-Ginsbach; A. J. Grau

    2004-01-01

    Microbial agents may play a role in the pathogenesis of multiple sclerosis (MS). C. pneumoniae has been recently associated with MS; however, study results are at variance. We tested the hypothesis that Chlamydia pneumoniae-specific DNA and RNA are more often detected in cerebrospinal fluid (CSF) of patients with multiple sclerosis than patients with other neurological diseases (OND). We investigated CSF

  12. Effects of Age on Cerebrospinal Fluid Oxytocin Levels in Free-Ranging Adult Female and Infant Rhesus Macaques

    E-print Network

    Maestripieri, Dario

    Effects of Age on Cerebrospinal Fluid Oxytocin Levels in Free-Ranging Adult Female and Infant University of Chicago There is growing interest in examining oxytocin and social functioning in human and non-human primates. Studies of human oxytocin biology are typically restricted to peripheral assessments because

  13. Cerebrospinal fluid S-adenosylmethionine in depression and dementia: effects of treatment with parenteral and oral S-adenosylmethionine

    Microsoft Academic Search

    T Bottiglieri; P Godfrey; T Flynn; M W Carney; B K Toone; E H Reynolds

    1990-01-01

    Cerebrospinal fluid (CSF) S-adenosylmethionine (SAM) levels were significantly lower in severely depressed patients than in a neurological control group. The administration of SAM either intravenously or orally is associated with a significant rise of CSF SAM, indicating that it crosses the blood-brain barrier in humans. These observations provide a rational basis for the antidepressant effect of SAM, which has been

  14. Interleukin6 released in human cerebrospinal fluid following traumatic brain injury may trigger nerve growth factor production in astrocytes

    Microsoft Academic Search

    Thomas Kossmann; Volkmar Hans; Hans-Georg Imhof; Otmar Trentz; Maria Cristina Morganti-Kossmann

    1996-01-01

    Cytokines are involved in nerve regeneration by modulating the synthesis of neurotrophic factors. The role played by interleukin-6 (IL-6) in promoting nerve growth factor (NGF) after brain injury was investigated by monitoring the release of IL-6 and NGF in ventricular cerebrospinal fluid (CSF) of 22 patients with severe traumatic brain injuries. IL-6 was found in the CSF of all individuals

  15. Detection of Aspergillus DNA in Cerebrospinal Fluid from Patients with Cerebral Aspergillosis by a Nested PCR Assay

    Microsoft Academic Search

    M. Hummel; B. Spiess; K. Kentouche; S. Niggemann; C. Bohm; S. Reuter; M. Kiehl; H. Morz; R. Hehlmann; D. Buchheidt

    2006-01-01

    Invasive aspergillosis (IA), a complication with high mortality rates, especially in disseminated IA with cerebral involvement, is difficult to diagnose. Biopsy of cerebral lesions is often not feasible, and culture of Aspergillus spp. from cerebrospinal fluid (CSF) is frequently negative. New molecular methods have emerged for diagnosing IA. So far, there are only few reports of Aspergillus DNA detection in

  16. Resistance to outflow of cerebrospinal fluid after central infusions of angiotensin

    NASA Technical Reports Server (NTRS)

    Morrow, B. A.; Keil, L. C.; Severs, W. B.

    1992-01-01

    Infusions of artificial cerebrospinal fluid (CSF) into the cerebroventricles of conscious rats can raise CSF pressure (CSFp). This response can be modified by some neuropeptides. One of these, angiotensin, facilitates the rise in CSFp. We measured CSFp in conscious rats with a computerized system and evaluated resistance to CSF outflow during infusion of artificial CSF, with or without angiotensin, from the decay kinetics of superimposed bolus injections. Angiotensin (10 ng/min) raised CSFp (P less than 0.05) compared with solvent, but the resistance to CSF outflow of the two groups was similar (P greater than 0.05). Because CSFp was increased by angiotensin without an increase in the outflow resistance, a change in some volume compartment is likely. Angiotensin may raise CSFp by increasing CSF synthesis; this possibility is supported, since the choroid plexuses contain an intrinsic isorenin-angiotensin system. Alternatively, angiotensin may dilate pial arteries, leading to an increased intracranial blood volume.

  17. The serum and cerebrospinal fluid pharmacokinetics of anakinra after intravenous administration to non-human primates.

    PubMed

    Fox, Elizabeth; Jayaprakash, Nalini; Pham, Tuyet-Hang; Rowley, Ayana; McCully, Cynthia L; Pucino, Frank; Goldbach-Mansky, Raphaela

    2010-06-01

    Anakinra improves the central nervous system manifestations of neonatal-onset multisystem inflammatory disease, which is mediated by IL-1beta oversecretion. The cerebrospinal fluid (CSF) penetration of the IL-1 receptor antagonist anakinra was studied in rhesus monkeys after intravenous doses of 3 and 10 mg/kg. Drug exposure (area under concentration-time curve) in CSF was 0.28% of that in serum. The average CSF concentration at 3 mg/kg was 1.8 ng/mL, which is 30-fold higher than endogenous CSF levels of IL-1Ra. The CSF penetration was not dose-dependent, indicating that the CSF penetration was not saturated in the 3 to 10 mg/kg dose range. PMID:20421138

  18. Cerebrospinal fluid dynamics of the cava septi pellucidi and vergae. Case report.

    PubMed

    Sencer, A; Sencer, S; Turantan, I; Devecio?lu, O

    2001-01-01

    This case involved a 26-month-old boy who had recurrent hemorrhagic venous infarction caused by venous sinus occlusion. Distension and enlargement of the cavum septi pellucidi (CSP) and cavum vergae (CV), along with hydrocephalus, was detected during the course of the disease and was observed to regress together with resolution of the venous occlusion. Venous hypertension caused by sinus occlusion was thought to be responsible for the disturbed resorption of cerebrospinal fluid (CSF) in the CSP and CV in this patient. This case is unique because it is the first one to support the hypothesis of resorption of CSF in the cava by a pressure gradient involving the septal capillaries and veins. PMID:11147881

  19. The cerebrospinal fluid provides a proliferative niche for neural progenitor cells

    PubMed Central

    Lehtinen, Maria K.; Zappaterra, Mauro W.; Chen, Xi; Yang, Yawei J.; Hill, Anthony; Lun, Melody; Maynard, Thomas; Gonzalez, Dilenny; Kim, Seonhee; Ye, Ping; D’Ercole, A. Joseph; Wong, Eric T.; LaMantia, Anthony S.; Walsh, Christopher A.

    2011-01-01

    Cortical development depends on the active integration of cell autonomous and extrinsic cues, but the coordination of these processes is poorly understood. Here, we show that the apical complex protein Pals1 and Pten have opposing roles in localizing the Igf1R to the apical, ventricular domain of cerebral cortical progenitor cells. We found that the cerebrospinal fluid (CSF), which contacts this apical domain, has an age-dependent effect on proliferation, much of which is attributable to Igf2, but that CSF contains other signaling activities as well. CSF samples from patients with glioblastoma multiforme show elevated Igf2 and stimulate stem cell proliferation in an Igf2-dependent manner. Together, our findings demonstrate that the apical complex couples intrinsic and extrinsic signaling, enabling progenitors to sense and respond appropriately to diffusible CSF-borne signals distributed widely throughout the brain. The temporal control of CSF composition may have critical relevance to normal development and neuropathological conditions. PMID:21382550

  20. Cerebrospinal fluid biomarkers of Alzheimer’s disease in cognitively healthy elderly

    PubMed Central

    Randall, Catherine; Mosconi, Lisa; de Leon, Mony; Glodzik, Lidia

    2014-01-01

    Numerous studies have shown that Alzheimer’s Disease (AD) pathology begins before the onset of clinical symptoms. Because therapies are likely to be more effective if they are implemented early in the disease progression, it is necessary to identify reliable biomarkers to detect AD pathology in the early stages of the disease, ideally in presymptomatic individuals. Recent research has identified three candidate cerebrospinal fluid (CSF) biomarkers that reflect AD pathology: amyloid beta (Aß42), total tau protein (t-tau), and tau protein phosphorylated at AD-specific epitopes (p-tau). They are useful in supporting the AD diagnosis and have predictive value for AD when patients are in the stage of mild cognitive impairment (MCI). However, their predictive utility in cognitively healthy subjects is still being evaluated. We conducted a review of studies published between 1993 and 2011 and summarized their findings on the role of CSF biomarkers for AD in healthy elderly. PMID:23747874

  1. Catecholamines and their major metabolites in plasma and cerebrospinal fluid of man.

    PubMed

    Vlachakis, N D; Lampano, C; Alexander, N; Maronde, R F

    1981-12-14

    In 36 patients undergoing elective surgery under spinal anesthesia, plasma and cerebrospinal fluid (CSF) concentrations of catecholamines and their major metabolic products were determined. The development of specific and sensitive radioenzymatic assays make these determinations possible. The levels of norepinephrine, epinephrine, and the O-methylated metabolite, normetanephrine, were greater in the plasma then the CSF, although the difference was significant for norepinephrine and epinephrine only (P less than 0.01 for both) On the other hand the levels of both deaminated metabolites dihydroxyphenylglycol (DOPEG) and dihydroxymandelic acid (DOMA) were greater in the CSF the in plasma, but the difference was significant for DOPEG only (P less than 0.01). Although there was a positive and significant correlation between the levels in plasma and CSF of all these compounds, their concentrations in CSF may reflect metabolism of catecholamines in the central nervous system. PMID:7306812

  2. The Choroid Plexus and Cerebrospinal Fluid: Emerging Roles in Development, Disease, and Therapy

    PubMed Central

    Bjornsson, Christopher S.; Dymecki, Susan M.; Gilbertson, Richard J.; Holtzman, David M.

    2013-01-01

    Although universally recognized as the source of cerebrospinal fluid (CSF), the choroid plexus (ChP) has been one of the most understudied tissues in neuroscience. The reasons for this are multiple and varied, including historical perceptions about passive and permissive roles for the ChP, experimental issues, and lack of clinical salience. However, recent work on the ChP and instructive signals in the CSF have sparked new hypotheses about how the ChP and CSF provide unexpected means for regulating nervous system structure and function in health and disease, as well as new ChP-based therapeutic approaches using pluripotent stem cell technology. This minisymposium combines new and established investigators to capture some of the newfound excitement surrounding the ChP-CSF system. PMID:24198345

  3. Normal pressure hydrocephalus. Influences on cerebral hemodynamic and cerebrospinal fluid pressure--chemical autoregulation

    SciTech Connect

    Meyer, J.S.; Tachibana, H.; Hardenberg, J.P.; Dowell, R.E. Jr.; Kitagawa, Y.; Mortel, K.F.

    1984-02-01

    Blood flow in the cerebral gray matter was measured in normal pressure hydrocephalus and Alzheimer disease by 133Xe inhalation. Flow values in the frontal and temporal gray matter increased after lowering cerebrospinal fluid (CSF) pressure by lumbar puncture in normal pressure hydrocephalus (p less than 0.05) and also after shunting. One case with cerebral complications did not improve clinically. In Alzheimer disease the reverse (decreases in flow in the gray matter) occurred after removal of CSF. Normal pressure hydrocephalus was associated with impaired cerebral vasomotor responsiveness during 100% oxygen and 5% carbon dioxide inhalation. This complication was restored toward normal after CSF removal and/or shunting. Cerebral blood flow measurements appear to be useful for confirming the diagnosis of normal pressure hydrocephalus and predicting the clinical benefit from shunting.

  4. Plasma oxytocin and vasopressin do not predict neuropeptide concentrations in human cerebrospinal fluid.

    PubMed

    Kagerbauer, S M; Martin, J; Schuster, T; Blobner, M; Kochs, E F; Landgraf, R

    2013-07-01

    The involvement of the neuropeptides oxytocin (OXT) and vasopressin (AVP) in human socio-emotional behaviours is attracting increasing attention. There is ample evidence for elevated plasma levels upon a wide variety of social and emotional stimuli and scenarios, ranging from romantic love via marital distress up to psychopathology, with cause versus consequence being largely unclear. The present study examined whether plasma levels of both OXT and AVP are reflective of central neuropeptide levels, as assumed to impact upon socio-emotional behaviours. Concomitant plasma and cerebrospinal fluid (CSF) samples were taken from 41 non-neurological and nonpsychiatric patients under basal conditions. Although OXT and AVP levels in the CSF exceeded those in plasma, there was no correlation between both compartments, clearly suggesting that plasma OXT and AVP do not predict central neuropeptide concentrations. Thus, the validity of plasma OXT and AVP as potential biomarkers of human behaviour needs further clarification. PMID:23574490

  5. Effects of aluminum chloride on the rate of secretion of the cerebrospinal fluid

    SciTech Connect

    Zlokovic, B.V.; Davson, H.; Preston, J.E.; Segal, M.B.

    1987-11-01

    The claim that AlCl/sub 3/ could produce 100% inhibition of cerebrospinal fluid secretion was investigated using ventriculocisternal perfusion in the rabbit, and it was shown that a large part of this inhibition was an artefact due to a pH sensitivity of Blue Dextran, used as an indiffusible marker, caused by AlCl/sub 3/. Thus the true inhibition found, using (/sup 3/H)labeled markers, was about 33% and usually only partly reversible. Penetration of /sup 22/Na from blood into the perfused ventricles was partially inhibited by AlCl/sub 3/. The effects of some other acid buffer systems, namely acetate and phosphate, on rate of secretion were measured; the results were highly variable. When mean arterial pressure was measured, it was found to be unaffected by AlCl/sub 3/ but elevated with acetate and phosphate buffer mixtures.

  6. Hydrocephalus communicans after traumatic upper cervical spine injury with a cerebrospinal fluid fistula: a rare complication

    PubMed Central

    Mica, Ladislav; Neuhaus, Valentin; Pöschmann, Enrico; Könü-Leblebicioglu, Dilek; Schwarz, Urs; Wanner, Guido A; Werner, Clément ML; Simmen, Hans-Peter

    2010-01-01

    Secondary hydrocephalus communicans after traumatic upper cervical spine injuries with leakage of cerebrospinal fluid is a rare and hardly described complication. A case of a 75-year-old woman sustained a type II dens axis without other injuries, especially without evidence of a hydrocephalus in the primary CT scan. Dorsal atlanto-axial fusion was performed. Postoperative drainage was prolonged and positive for ?2-transferrin. Wound revision with an attempt to seal the leakage was not successful. Secondary CT scans of the brain were performed due to neurological deterioration and showed a hydrocephalus with typical EEG findings. No anatomical reason for a circulative obstruction was found in the CT scan. After application of a ventriculo-peritoneal shunt the neurological status improved and the patient could be discharged to neurological rehabilitation. PMID:22752831

  7. Identification of Biomarkers in Cerebrospinal Fluid and Serum of Multiple Sclerosis Patients by Immunoproteomics Approach

    PubMed Central

    Colomba, Paolo; Fontana, Simona; Salemi, Giuseppe; Barranca, Marilisa; Lo Sicco, Claudia; Mazzola, Maria Antonietta; Ragonese, Paolo; Savettieri, Giovanni; De Leo, Giacomo; Alessandro, Riccardo; Duro, Giovanni

    2014-01-01

    Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system. At present, the molecular mechanisms causing the initiation, development and progression of MS are poorly understood, and no reliable proteinaceous disease markers are available. In this study, we used an immunoproteomics approach to identify autoreactive antibodies in the cerebrospinal fluid of MS patients to use as candidate markers with potential diagnostic value. We identified an autoreactive anti-transferrin antibody that may have a potential link with the development and progression of MS. We found this antibody at high levels also in the serum of MS patients and created an immunoenzymatic assay to detect it. Because of the complexity and heterogeneity of multiple sclerosis, it is difficult to find a single marker for all of the processes involved in the origin and progression of the disease, so the development of a panel of biomarkers is desirable, and anti-transferrin antibody could be one of these. PMID:25517032

  8. Cerebrospinal fluid levels of phenylacetic acid in mental illness: behavioral associations and response to neuroleptic treatment.

    PubMed

    Sharma, R P; Faull, K; Javaid, J I; Davis, J M

    1995-05-01

    Cerebrospinal fluid levels of phenylacetic acid (CSF PAA) were obtained from normal controls and from drug-free psychiatric inpatients (schizophrenia, major depression, mania, and schizoaffective disorder). Post-treatment CSF PAA levels were obtained from 16 patients after 4 weeks of neuroleptic treatment. Phenylacetic acid levels were higher in women and were significantly correlated with age. There were no differences in CSF PAA levels between the various diagnostic groups and no difference between the paranoid and the nonparanoid subtypes of schizophrenia. CSF PAA was significantly correlated with several measures of psychopathology, especially the Brief Psychiatric Rating Scale hostility/suspiciousness factor. Neuroleptic treatment did not result in significant PAA changes. These findings are discussed in light of the amphetamine-like role ascribed to phenylethylamine, the precursor of PAA. PMID:7639084

  9. Nicotinamide-N-methyltransferase is higher in the lumbar cerebrospinal fluid of patients with Parkinson's disease.

    PubMed

    Aoyama, K; Matsubara, K; Kondo, M; Murakawa, Y; Suno, M; Yamashita, K; Yamaguchi, S; Kobayashi, S

    2001-01-26

    Parkinson's disease (PD) may be initiated or precipitated by endogenous toxins with a structure similar to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in genetically-predisposed individuals. Nicotinamide N-methyltransferase (NNMT) catalyzes N-methylation of nicotinamide and other pyridines to form pyridinium ions. The protein amount of NNMT was measured in the lumbar cerebrospinal fluid of PD patients by immunoblot analysis using anti-human NNMT antibody. In younger (65 years old or younger) PD patients, the relative level of NNMT protein was significantly higher than that in younger controls. The NNMT protein was significantly affected by aging: the amount decreased along with aging in PD patients. These findings suggested that excess NNMT in the central nervous system might be implicated in the PD pathogenesis. PMID:11154840

  10. Pseudocholinesterase activity in cerebrospinal fluid as a biomarker of solid central nervous system tumors in children

    PubMed Central

    Mikecin, Lili; Križmari?, Miljenko; Stepan Giljevi?, Jasminka; Gjurašin, Miroslav; Kern, Josipa; Leni?ek Krleža, Jasna; Popovi?, Ljiljana

    2013-01-01

    Aim To determine the activity of pseudocholinesterase (PChE) in cerebrospinal fluid (CSF) and serum in children with solid central nervous system (CNS) tumor and to assess whether PChE activity could be a valid biomarker for solid CNS tumors in children. Methods The study and control group included 30 children each. Children in the study group had a solid CNS tumor, while those from the control group had never suffered from any tumor diseases. CSF and serum samples were collected from all participants and PChE activity was determined using the Ellman’s spectrophotometric method. PChE activity in CSF was shown as a cerebrospinal fluid/serum ratio expressed in percentage, ie, PChE CSF/serum ratio. Receiver operating characteristic (ROC) curve was used to assess whether PChE activity can be used as a biomarker for identifying children with solid CNS tumors. Results Children with solid CNS tumor had significantly higher PChE activity in CSF and serum, as well as PChE CSF/serum ratio (P?=?0.001). PChE CSF/serum ratio in the study group was 2.38% (interquartile range [IQR] 1.14-3.97) and 1.09% (IQR 0.95-1.45) in the control group. ROC curve analysis of PChE CSF/serum ratio resulted in an area under the curve (AUC) value of 0.76 (95% confidence interval [CI] 0.63-0.88) and a cut-off of 1.09. Twenty five of 29 patients with elevated PChE CSF/serum ratio had a tumor, corresponding to a sensitivity of 83% and a specificity of 53%. Conclusion PChE CSF/serum ratio may be used as a test or biomarker with good sensitivity for solid CNS tumors in children. PMID:24170721

  11. Commentary: Unnecessary preoperative epidural steroid injections lead to cerebrospinal fluid leaks confirmed during spinal stenosis surgery

    PubMed Central

    Epstein, Nancy E.

    2014-01-01

    Background: Increasingly, older patients with severe spinal stenosis/instability undergo multiple unnecessary preoperative epidural spinal injections (ESI), despite their risks and lack of long-term benefits. Here we add to the list of risks by showing how often preoperative ESI lead to punctate cerebrospinal fluid (CSF) fistulas documented during subsequent surgery (e.g. multilevel laminectomies with non-instrumented fusions). Methods: A series of 39 patients with spinal stenosis/instability prospectively underwent multilevel laminectomy/non-instrumented fusion utilizing lamina autograft and NanOss Bioactive. We asked how often preoperative ESI were performed in this population and how frequently they contributed to operatively confirmed punctate cerebrospinal fluid (CSF) fistulas. Notably, CSF leaks were clearly attributed to ESI, as they were located centrally/paracentrally at the L4-L5 level, just below hypertrophied/ossified yellow ligament (OYL), and were the exact size of a Tuohy needle with clean edges. Results: An average of 4.1 (range 2-12) preoperative ESI were performed in 33 of 39 patients undergoing average 4.3 level laminectomies and 1.3 level non-instrumented fusions; 6 (18.2%) patients exhibited operatively confirmed, punctate CSF fistulas attributed to these ESI. The most recent injections were administered between 2 and 5 weeks prior to surgery (average 3.9 weeks). Fistulas were primarily repaired with 7-0 GORE-TEX sutures and fibrin Sealant (Tisseel). Conclusions: Of 33 patients undergoing multilevel laminectomies with non-instrumented fusions receiving preoperative ESI, 6 (18.2%) had operatively confirmed punctate CSF fistulas due to preoperative ESI performed an average of 4.1 times per patient. PMID:25289153

  12. Pregnancy influences the plasma pharmacokinetics but not the cerebrospinal fluid pharmacokinetics of raltegravir: a preclinical investigation.

    PubMed

    Mahat, Mahamad Yunnus A; Thippeswamy, B S; Khan, Farhin R; Edunuri, Ramya; Nidhyanandan, Saranya; Chaudhary, Shilpee

    2014-12-18

    Alterations in antiretroviral pharmacokinetics during pregnancy must be understood for the drugs to be used safely and effectively. Present study is an attempt to understand the potential changes in raltegravir plasma and cerebrospinal fluid pharmacokinetics during pregnancy in late pregnant and non-pregnant rats. In vitro plasma protein binding, metabolic stability, intravenous blood-brain barrier (BBB) permeability and oral pharmacokinetic studies were performed. Raltegravir concentrations in different matrices were measured using LC-MS/MS. Raltegravir plasma protein binding remained similar in both groups, whereas, metabolic stability was significantly lower in pregnant rats than the non-pregnant rats liver microsomes. In oral pharmacokinetic study, peak plasma concentrations and systemic exposures were significantly lower (?37%) and clearance was significantly higher (?61%) in late pregnant rats compared to non-pregnant rats. However, unlike plasma pharmacokinetics, CSF pharmacokinetic profile of raltegravir was similar in both pregnant and non-pregnant rats. Following intravenous administration, raltegravir showed higher BBB permeability in pregnant rats compared to non-pregnant rats. But the mean CSF-to-plasma ratio was significantly higher in pregnant rats compared to non-pregnant rats suggesting higher brain penetration in pregnant rats. In conclusion, pregnancy significantly affected the plasma pharmacokinetics, whereas cerebrospinal fluid pharmacokinetics remained fairly similar in pregnant and non-pregnant rats. Although current plasma pharmacokinetic data is in contradiction to the reported human data, pregnancy-specific pharmacokinetic changes observed in the current study emphasize the need for close therapeutic monitoring while treating the pregnant population and also warrants the need for additional clinical data with larger group of patients. PMID:25195836

  13. Alterations in Protein Regulators of Neurodevelopment in the Cerebrospinal Fluid of Infants with Posthemorrhagic Hydrocephalus of Prematurity*

    PubMed Central

    Morales, Diego M.; Townsend, R. Reid; Malone, James P.; Ewersmann, Carissa A.; Macy, Elizabeth M.; Inder, Terrie E.; Limbrick, David D.

    2012-01-01

    Neurological outcomes of preterm infants with posthemorrhagic hydrocephalus are among the worst in newborn medicine. There remains no consensus regarding the diagnosis or treatment of posthemorrhagic hydrocephalus, and the pathological pathways leading to the adverse neurological sequelae are poorly understood. In the current study, we developed an innovative approach to simultaneously identify potential diagnostic markers of posthemorrhagic hydrocephalus and investigate novel pathways of posthemorrhagic hydrocephalus-related neurological disability. Tandem multi-affinity fractionation for specific removal of plasma proteins from the hemorrhagic cerebrospinal fluid samples was combined with high resolution label-free quantitative proteomics. Analysis of cerebrospinal fluid obtained from infants with posthemorrhagic hydrocephalus demonstrated marked differences in the levels of 438 proteins when compared with cerebrospinal fluid from age-matched control infants. Amyloid precursor protein, neural cell adhesion molecule-L1, neural cell adhesion molecule-1, brevican and other proteins with important roles in neurodevelopment showed profound elevations in posthemorrhagic hydrocephalus cerebrospinal fluid compared with control. Initiation of neurosurgical treatment of posthemorrhagic hydrocephalus resulted in resolution of these elevations. The results from this foundational study demonstrate the significant promise of tandem multi-affinity fractionation-proteomics in the identification and quantitation of protein mediators of neurodevelopment and neurological injury. More specifically, our results suggest that cerebrospinal fluid levels of proteins such as amyloid precursor protein or neural cell adhesion molecule-L1 should be investigated as potential diagnostic markers of posthemorrhagic hydrocephalus. Notably, dysregulation of the levels these and other proteins may directly affect ongoing neurodevelopmental processes in these preterm infants, providing an entirely new hypothesis for the developmental disability associated with posthemorrhagic hydrocephalus. PMID:22186713

  14. Alterations in cerebrospinal fluid glycerophospholipids and phospholipase A2 activity in Alzheimer's disease[S

    PubMed Central

    Fonteh, Alfred N.; Chiang, Jiarong; Cipolla, Matthew; Hale, Jack; Diallo, Fatimatou; Chirino, Alejandra; Arakaki, Xianghong; Harrington, Michael G.

    2013-01-01

    Our aim is to study selected cerebrospinal fluid (CSF) glycerophospholipids (GP) that are important in brain pathophysiology. We recruited cognitively healthy (CH), minimally cognitively impaired (MCI), and late onset Alzheimer's disease (LOAD) study participants and collected their CSF. After fractionation into nanometer particles (NP) and supernatant fluids (SF), we studied the lipid composition of these compartments. LC-MS/MS studies reveal that both CSF fractions from CH subjects have N-acyl phosphatidylethanolamine, 1-radyl-2-acyl-sn-glycerophosphoethanolamine (PE), 1-radyl-2-acyl-sn-glycerophosphocholine (PC), 1,2-diacyl-sn-glycerophosphoserine (PS), platelet-activating factor-like lipids, and lysophosphatidylcholine (LPC). In the NP fraction, GPs are enriched with a mixture of saturated, monounsaturated, and polyunsaturated fatty acid species, while PE and PS in the SF fractions are enriched with PUFA-containing molecular species. PC, PE, and PS levels in CSF fractions decrease progressively in participants from CH to MCI, and then to LOAD. Whereas most PC species decrease equally in LOAD, plasmalogen species account for most of the decrease in PE. A significant increase in the LPC-to-PC ratio and PLA2 activity accompanies the GP decrease in LOAD. These studies reveal that CSF supernatant fluid and nanometer particles have different GP composition, and that PLA2 activity accounts for altered GPs in these fractions as neurodegeneration progresses. PMID:23868911

  15. Cisterna magna microdialysis of sup 22 Na to evaluate ion transport and cerebrospinal fluid dynamics

    SciTech Connect

    Knuckey, N.W.; Fowler, A.G.; Johanson, C.E.; Nashold, J.R.; Epstein, M.H. (Brown Univ./Rhode Island Hospital, Providence (USA))

    1991-06-01

    Microdialysis is used in vivo for measuring compounds in brain interstitial fluid. The authors describe another application of this technique to the central nervous system, namely microprobe dialysis in the cisterna magna to study the dynamics of ion transport and cerebrospinal fluid (CSF) formation in the rat. The choroid plexus is the major source of CSF, which is produced by active transport of Na from blood into the cerebral ventricles. Formation of CSF is directly proportional to the blood-to-CSF transport of Na. By injecting {sup 22}Na into the systemic circulation and quantifying its movement into CSF by microdialysis, one can reliably estimate alterations in the rate of CSF formation. The sensitivity of this system was determined by administering acetazolamide, a standard inhibitor of CSF production. Because acetazolamide is known to decrease CSF formation by 40% to 50%, the cisternal microdialysis system in animals treated with this drug should detect a corresponding decrease in the amount of {sup 22}Na dialyzed. This hypothesis is supported by the {sup 22}Na uptake curves for control versus treated animals: that is, by the acetazolamide-induced average diminution of about 45% in both the rate and extent of tracer accession to dialysate. Bumetanide, a loop diuretic, reduced by 30% the {sup 22}Na entry into dialysate. Microprobe dialysis of fluid in the cisterna magna is thus a minimally invasive and economical method for evaluating effects of drugs and hormones on the choroid plexus-CSF system.

  16. Effects of irregular cerebrospinal fluid production rate in human brain ventricular system

    NASA Astrophysics Data System (ADS)

    Hadzri, Edi Azali; Shamsudin, Amir Hamzah; Osman, Kahar; Abdul Kadir, Mohammed Rafiq; Aziz, Azian Abd

    2012-06-01

    Hydrocephalus is an abnormal accumulation of fluid in the ventricles and cavities in the brain. It occurs when the cerebrospinal fluid (CSF) flow or absorption is blocked or when excessive CSF is secreted. The excessive accumulation of CSF results in an abnormal widening of the ventricles. This widening creates potentially harmful pressure on the tissues of the brain. In this study, flow analysis of CSF was conducted on a three-dimensional model of the third ventricle and aqueduct of Sylvius, derived from MRI scans. CSF was modeled as Newtonian Fluid and its flow through the region of interest (ROI) was done using EFD. Lab software. Different steady flow rates through the Foramen of Monro, classified by normal and hydrocephalus cases, were modeled to investigate its effects. The results show that, for normal and hydrocephalus cases, the pressure drop of CSF flow across the third ventricle was observed to be linearly proportionally to the production rate increment. In conclusion, flow rates that cause pressure drop of 5 Pa was found to be the threshold for the initial sign of hydrocephalus.

  17. [Continuous occurrence of two cases of Haemophilus influenzae type b meningitis caused by different strains in a day nursery].

    PubMed

    Hoshino, Tadashi; Nakamura, Akira; Ishikawa, Nobuyasu; Ishiwada, Naruhiko; Kohno, Yoichi

    2003-08-01

    Two cases of Haemophilus influenzae type b (Hib) meningitis were occurred continuously in a day nursery. Both isolates obtained from cerebrospinal fluids of 2 patients were beta lactamase producing amoxicillin/clavulanic acid sensitive strains. But biotypes and restriction fragment length polymorphism patterns by SmaI digested pulse-field gel electrophoresis of two isolates were different, respectively. Although it was already reported simultaneous occurrence of two cases of Hib meningitis caused by same strain through the nursery contact, none were reported by different strains. It was considered that two colonized strains had caused meningitis in two patients continuously. PMID:14515758

  18. Recurrent meningitis with upper airway obstruction in a child: frontonasal encephalocele- a case report.

    PubMed

    Sachdeva, Soumya; Kapoor, Rohit; Paul, Premila; Yadav, Rakesh

    2014-08-01

    Nasal encephalocele are rare congenital anomalies; these benign masses may be confused with nasal dermoids, hemangiomas, nasal gliomas and anterior skull base masses. These lesions have concomitant defects in the anterior cranial fossa thus this potential communication can cause recurrent episodes of meningitis and/or difficulty in breathing and cosmetic anomalies. We bring a case of a 6-year-old child who presented to the clinic with multiple episodes of meningitis which was associated with nasal discharge. The imaging studies and nasal fluid analysis confirmed it as cerebrospinal fluid; subsequently imaging findings concluded it as frontonasal encephalocele which was later resected and patient showed improvement. PMID:25302244

  19. Detection of Protein Aggregates in Brain and Cerebrospinal Fluid Derived from Multiple Sclerosis Patients

    PubMed Central

    David, Monique Antoinette; Tayebi, Mourad

    2014-01-01

    Studies of the properties of soluble oligomer species of amyloidogenic proteins, derived from different proteins with little sequence homology, have indicated that they share a common structure and may share similar pathogenic mechanisms. Amyloid ?, tau protein, as well as amyloid precursor protein normally associated with Alzheimer’s disease and Parkinson’s disease were found in lesions and plaques of multiple sclerosis patients. The objective of the study is to investigate whether brain and cerebrospinal fluid (CSF) samples derived from multiple sclerosis patients demonstrate the presence of soluble oligomers normally associated with protein-misfolding diseases such as Alzheimer’s disease. We have used anti-oligomer monoclonal antibodies to immunodetect soluble oligomers in CSF and brain tissues derived from multiple sclerosis patients. In this report, we describe the presence of soluble oligomers in the brain tissue and cerebral spinal fluid of multiple sclerosis patients detected with our monoclonal anti-oligomer antibodies with Western blot and Sandwich enzyme-linked immunosorbent assay (sELISA). These results might suggest that protein aggregation plays a role in multiple sclerosis pathogenesis although further and more refined studies are needed to confirm the role of soluble aggregates in multiple sclerosis. PMID:25520699

  20. The role of cerebrospinal fluid pressure in glaucoma and other ophthalmic diseases: A review

    PubMed Central

    Fleischman, David; Allingham, R. Rand

    2013-01-01

    Glaucoma is one of the most common causes of blindness in the world. Well-known risk factors include age, race, a positive family history and elevated intraocular pressures. A newly proposed risk factor is decreased cerebrospinal fluid pressure (CSFP). This concept is based on the notion that a pressure differential exists across the lamina cribrosa, which separates the intraocular space from the subarachnoid fluid space. In this construct, an increased translaminar pressure difference will occur with a relative increase in elevated intraocular pressure or a reduction in CSFP. This net change in pressure is proposed to act on the tissues within the optic nerve head, potentially contributing to glaucomatous optic neuropathy. Similarly, patients with ocular hypertension who have elevated CSFPs, would enjoy a relatively protective effect from glaucomatous damage. This review will focus on the current literature pertaining to the role of CSFP in glaucoma. Additionally, the authors examine the relationship between glaucoma and other known CSFP-related ophthalmic disorders. PMID:24227969

  1. Cerebrospinal fluid ionic regulation, cerebral blood flow, and glucose use during chronic metabolic alkalosis

    SciTech Connect

    Schroeck, H.K.; Kuschinsky, W. (Univ. of Bonn (Germany, F.R.))

    1989-10-01

    Chronic metabolic alkalosis was induced in rats by combining a low K+ diet with a 0.2 M NaHCO3 solution as drinking fluid for either 15 or 27 days. Local cerebral blood flow and local cerebral glucose utilization were measured in 31 different structures of the brain in conscious animals by means of the iodo-(14C)antipyrine and 2-(14C)deoxy-D-glucose method. The treatment induced moderate (15 days, base excess (BE) 16 mM) to severe (27 days, BE 25 mM) hypochloremic metabolic alkalosis and K+ depletion. During moderate metabolic alkalosis no change in cerebral glucose utilization and blood flow was detectable in most brain structures when compared with controls. Cerebrospinal fluid (CSF) K+ and H+ concentrations were significantly decreased. During severe hypochloremic alkalosis, cerebral blood flow was decreased by 19% and cerebral glucose utilization by 24% when compared with the control values. The decrease in cerebral blood flow during severe metabolic alkalosis is attributed mainly to the decreased cerebral metabolism and to a lesser extent to a further decrease of the CSF H+ concentration. CSF K+ concentration was not further decreased. The results show an unaltered cerebral blood flow and glucose utilization together with a decrease in CSF H+ and K+ concentrations at moderate metabolic alkalosis and a decrease in cerebral blood flow and glucose utilization together with a further decreased CSF H+ concentration at severe metabolic alkalosis.

  2. Reversible cerebrospinal fluid edema and porencephalic cyst, a rare complication of ventricular catheter.

    PubMed

    Ozeki, Michio; Funato, Michinori; Teramoto, Takahide; Ohe, Naoyuki; Asano, Takahiko; Kaneko, Hideo; Fukao, Toshiyuki; Kondo, Naomi

    2010-05-01

    Cerebrospinal fluid (CSF) edema and porencephaly are rare postoperative complications of a ventricular shunt that result from obstruction of the distal catheter, especially in children with taut ventricles. We report a 10-year-old male with cerebellar germinoma complicated by obstructive hydrocephalus. Ventriculopuncture was performed and an Ommaya reservoir was implanted at the right frontal horn. A distal catheter was initially attached to the reservoir for drainage of hydrocephalus but was later removed. After surgery, multi-agent chemotherapy and radiation therapy, a brain MRI showed CSF edema and porencephaly in the right frontal white matter. These lesions were reduced by prompt removal of the ventricular catheter. It is important to recognize such complications and to remove the catheter as soon as possible, because the brain tissue affected by massive edema may develop irreversible changes. Advanced MRI techniques, including fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging may be helpful for assessing this pathological condition and its prognosis. PMID:20206530

  3. Mechanism of meningeal invasion by Neisseria meningitidis

    PubMed Central

    Coureuil, Mathieu; Join-Lambert, Olivier; Lécuyer, Hervé; Bourdoulous, Sandrine; Marullo, Stefano; Nassif, Xavier

    2012-01-01

    The blood-cerebrospinal fluid barrier physiologically protects the meningeal spaces from blood-borne bacterial pathogens, due to the existence of specialized junctional interendothelial complexes. Few bacterial pathogens are able to reach the subarachnoidal space and among those, Neisseria meningitidis is the one that achieves this task the most constantly when present in the bloodstream. Meningeal invasion is a consequence of a tight interaction of meningococci with brain endothelial cells. This interaction, mediated by the type IV pili, is responsible for the formation of microcolonies on the apical surface of the cells. This interaction is followed by the activation of signaling pathways in the host cells leading to the formation of endothelial docking structures resembling those elicited by the interaction of leukocytes with endothelial cells during extravasation. The consequence of these bacterial-induced signaling events is the recruitment of intercellular junction components in the docking structure and the subsequent opening of the intercellular junctions. PMID:22366962

  4. Reibergram of Intrathecal Synthesis of C4 in Patients with Eosinophilic Meningitis Caused by Angiostrongylus cantonensis

    PubMed Central

    Padilla-Docal, Bárbara; Dorta-Contreras, Alberto Juan; Bu-Coifiu-Fanego, Raisa; Rodríguez-Rey, Alexis; Gutiérrez-Hernández, Juan Carlos; de Paula-Almeida, Susana Olga

    2010-01-01

    Angiostrongylus cantonensis produces eosinophilic meningitis in humans and is endemic in Thailand, Taiwan, China, and the Caribbean region. During infection with this parasite, it is important to know if the complement system may be activated by the classical or lectin pathway. Cerebrospinal fluid and serum samples from 20 patients with meningitic angiostrongyliasis were used to quantify C4 levels and albumin. Results were plotted on a C4 CSF/serum quotient diagram or Reibergram. Twelve patients showed intrathecal synthesis of C4. Antibody-dependent complement cytotoxicity should be considered as a possible mechanism that destroys third-stage larvae of this helminth in cerebrospinal fluid of affected patients. PMID:20519605

  5. Properties of subependymal cerebrospinal fluid contacting neurones in the dorsal vagal complex of the mouse brainstem

    PubMed Central

    Orts-Del'Immagine, Adeline; Wanaverbecq, Nicolas; Tardivel, Catherine; Tillement, Vanessa; Dallaporta, Michel; Trouslard, Jérôme

    2012-01-01

    Cerebrospinal fluid (CSF) contacting neurones have been observed in various brain regions such as the hypothalamus, the dorsal nucleus of the raphe and around the central canal (cc) of the spinal cord but their functional role remains unclear. At the level of the spinal cord, subependymal cerebrospinal fluid contacting neurones (S-CSF-cNs) present a peculiar morphology with a soma close to the ependymal layer, a process projecting towards the cc and ending with a bud and a cilium. These neurones were recently shown to express polycystin kidney disease 2-like 1 (PKD2L1 or TRPP3) channels that are members of the polycystin subtype of the transient receptor potential (TRP) channel superfamily and that have been proposed as either chemo- or mechanoreceptors in several tissues. Using immunohistological techniques and whole-cell electrophysiological recordings in brain slices obtained from PKD2L1:EGFP transgenic adult mice, we looked for and determined the functional properties of S-CSF-cNs in the dorsal vagal complex (DVC), a hindbrain structure controlling autonomic functions such as blood pressure, energy balance and food intake. Here, we demonstrate that S-CSF-cNs received GABAergic and/or glycinergic synaptic entries and were also characterised by the presence of non-selective cationic channels of large conductance that could be detected even under whole-cell configuration. The channel activity was not affected by Psalmopoeus cambridgei toxin 1, a blocker of acid sensing ion channels (ASICs), but was blocked by amiloride and by a strong extracellular acidification. In contrast, extracellular alkalinisation and hypo-osmotic shocks increased channel activity. Based on these properties, we suggest that the single-channel activity recorded in medullar S-CSF-cNs is carried by PKD2L1 channels. Our study therefore reinforces the idea that PKD2L1 is a marker of S-CSF-cNs and points toward a role for S-CSF-cNs in the detection of circulating signals and of modifications in the extracellular environment. PMID:22570378

  6. The mediational effects of FDG hypometabolism on the association between cerebrospinal fluid biomarkers and neurocognitive function.

    PubMed

    Dowling, N Maritza; Johnson, Sterling C; Gleason, Carey E; Jagust, William J

    2015-01-15

    Positive cerebrospinal fluid (CSF) biomarkers of tau and amyloid beta42 suggest possible active underlying Alzheimer's disease (AD) including neurometabolic dysfunction and neurodegeneration leading to eventual cognitive decline. But the temporal relationship between CSF, imaging markers of neural function, and cognition has not been described. Using a statistical mediation model, we examined relationships between cerebrospinal fluid (CSF) analytes (hyperphosphorylated tau (p-Tau(181p)), ?-amyloid peptides 1-42 (A?(1-42)), total tau (t-Tau), and their ratios); change in cognitive function; and change in [18F]fluorodeoxyglucose (FDG) uptake using positron emission tomography (PET). We hypothesized that a) abnormal CSF protein values at baseline, result in cognitive declines by decreasing neuronal glucose metabolism across time, and b) the role of altered glucose metabolism in the assumed causal chain varies by brain region and the nature of CSF protein alteration. Data from 412 individuals participating in Alzheimer's Disease Neuroimaging (ADNI) cohort studies were included in analyses. At baseline, individuals were cognitively normal (N = 82), or impaired: 241 with mild cognitive impairment, and 89 with Alzheimer's disease. A parallel-process latent growth curve model was used to test mediational effects of changes in regional FDG-PET uptake over time in relation to baseline CSF biomarkers and changes in cognition, measured with the 13-item Alzheimer Disease's Assessment Scale-cognitive subscale (ADAS-Cog). Findings suggested a causal sequence of events; specifically, FDG hypometabolism acted as a mediator between antecedent CSF biomarker alterations and subsequent cognitive impairment. Higher baseline concentrations of t-Tau, and p-Tau(181p) were more predictive of decline in cerebral glucose metabolism than lower baseline concentrations of A?(1-42). FDG-PET changes appeared to mediate t-Tau or t-Tau/A?(1-42)-associated cognitive change across all brain regions examined. Significant direct effects of alterations in A?(1-42) levels on hypometabolism were observed in a single brain region: middle/inferior temporal gyrus. Results support a temporal framework model in which reduced CSF amyloid-related biomarkers occur earlier in the pathogenic pathway, ultimately leading to detrimental cognitive effects. Also consistent with this temporal framework model, baseline markers of neurofibrillary degeneration predicted changes in brain glucose metabolism in turn causing longitudinal cognitive changes, suggesting that tau-related burden precedes neurometabolic dysfunction. While intriguing, the hypothesized mediational relationships require further validation. PMID:25450107

  7. Three-dimensional cerebrospinal fluid flow within the human ventricular system.

    PubMed

    Howden, L; Giddings, D; Power, H; Aroussi, A; Vloeberghs, M; Garnett, M; Walker, D

    2008-04-01

    Cerebrospinal fluid (CSF) is a Newtonian fluid and can, therefore, be modelled using computational fluid dynamics (CFD). Previous modelling of the CSF has been limited to simplified geometric models. This work describes a geometrically accurate three dimensional (3D) computational model of the human ventricular system (HVS) constructed from magnetic resonance images (MRI) of the human brain. It is an accurate and full representation of the HVS and includes appropriately positioned CSF production and drainage locations. It was used to investigate the pulsatile motion of CSF within the human brain. During this investigation CSF flow rate was set at a constant 500 ml/day, to mimic real life secretion of CSF into the system, and a pulsing velocity profile was added to the inlets to incorporate the effect of cardiac pulsations on the choroid plexus and their subsequent influence on CSF motion in the HVS. Boundary conditions for the CSF exits from the ventricles (foramina of Magendie and Lushka) were found using a "nesting" approach, in which a simplified model of the entire central nervous system (CNS) was used to examine the effects of the CSF surrounding the ventricular system (VS). This model provided time varying pressure data for the exits from the VS nested within it. The fastest flow was found in the cerebral aqueduct, where a maximum velocity of 11.38 mm/s was observed over five cycles. The maximum Reynolds number recorded during the simulation was 15 with an average Reynolds number of the order of 0.39, indicating that CSF motion is creeping flow in most of the computational domain and consequently will follow the geometry of the model. CSF pressure also varies with geometry with a maximum pressure drop of 1.14 Pa occurring through the cerebral aqueduct. CSF flow velocity is substantially slower in the areas that are furthest away from the inlets; in some areas flow is nearly stagnant. PMID:18297492

  8. Neuraxial anesthesia in patients with intracranial hypertension or cerebrospinal fluid shunting systems: what should the anesthetist know?

    PubMed

    Guerci, P; Vial, F; Mcnelis, U; Losser, M R; Raft, J; Klein, O; Iohom, G; Audibert, G; Bouaziz, H

    2014-09-01

    The management of patients with central nervous system disorders such as brain tumours, hydrocephalus, intracranial hypertension, or subarachnoid hemorrhage has improved in recent years resulting in increased life expectancy. Consequently, the prevalence of patients with increased intracranial pressure or cerebrospinal fluid shunting devices presenting for non-neurological procedures has increased. These patients commonly receive a general anesthetic, as the safety profile of neuraxial anesthesia in this clinical setting remains uncertain. This article reviews literature on neuraxial anesthesia in patients with intracranial hypertension or cerebrospinal fluid shunting systems. It describes current knowledge, exposes and weighs the real benefits and risks of this technique in this setting. It provides several scenarios and anesthetic options to help the practitioner with choosing a tailored approach in this specific population. PMID:24280821

  9. Synergy of serum and cerebrospinal fluid antibodies against axonal cytoskeletal proteins in patients with different neurological diseases.

    PubMed

    Fialová, L; Bartos, A; Soukupová, J; Svarcová, J; Ridzon, P; Malbohan, I

    2009-01-01

    Autoantibodies against different axonal cytoskeletal proteins [the light (NFL) and medium (NFM) subunit of neurofilament and tubulin (TUB)] in serum and cerebrospinal fluid may be generated in response to the release of cytoskeleton from damaged neurons. We studied the relationships among these autoantibodies. Paired cerebrospinal fluid (CSF) and serum samples were obtained from 47 multiple sclerosis (MS) patients, 14 patients with neurodegenerative diseases, 21 patients with various neurological diseases and 16 normal control subjects. Levels of antibodies against NFL, NFM and TUB were related to each other in CSF in all groups, whereas close association of anti-cytoskeletal antibodies in serum was found in the MS group only. A concordant spectrum of anti-cytoskeletal antibodies is present in serum of MS patients, unlike in other neurological patients. The synergy between the spectrum of anti-cytoskeletal antibodies in serum and CSF might be one of the immunological features typical for the MS patients. PMID:19445843

  10. Calpain-like and lactate dehydrogenase activities in the cerebrospinal fluid of patients with amyotrophic lateral sclerosis

    Microsoft Academic Search

    L. V. Brylev; A. A. Yakovlev; M. V. Onufriev; M. N. Zakharova; I. A. Zavalishin; N. V. Gulyaeva

    2007-01-01

    Amyotrophic lateral sclerosis (ALS) is neurodegenerative disease accompanied by the death of motor neurons. To clarify the\\u000a role of calpain in the ALS-induced death of neurons, we measured the calpainlike and lactate dehydrogenase (LDH) activities\\u000a in the cerebrospinal fluid (CSF) of ALS patients and patients of a control group. The LDH activity measured in the CSF of\\u000a patients with ALS

  11. Modulators of cystein proteases and cell-death markers in the cerebrospinal fluid of patients with amyotrophic lateral sclerosis

    Microsoft Academic Search

    L. V. Brylev; E. N. Nelkina; A. A. Yakovlev; M. V. Onufriev; A. A. Shabalina; M. V. Kostyreva; M. N. Zakharova; I. A. Zavalishin; N. V. Gulyaeva

    2009-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective damage of motor\\u000a neurons in the brain and spinal cord. The aim of the current study was to reveal new specific markers of neurodegeneration\\u000a in the cerebrospinal fluid (CSF) of ALS patients. We measured the activities of substances that modulate the activity of cysteine\\u000a proteases (calpain, caspase, and

  12. Cerebrospinal fluid leakage after gamma knife radiosurgery for skull base metastasis from renal cell carcinoma: a case report.

    PubMed

    Kim, Chang-Hyun; Chung, Seung-Kyu; Dhong, Hun-Jong; Lee, Jung-Il

    2008-11-01

    We report a rare case of cerebrospinal fluid (CSF) leakage after radiosurgery for skull base metastasis from renal cell carcinoma. A mass invading the left petrous bone and sphenoid sinus was treated with gamma knife radiosurgery, and CSF rhinorrhea developed 4 months after the procedure. The CSF leak was successfully controlled by endoscopic sinus surgery. CSF leakage may develop as a rare complication after radiosurgery for skull base lesions, and the endoscopic repair technique is a useful therapeutic method. PMID:18797420

  13. Cerebrospinal fluid and blood flow in mild cognitive impairment and Alzheimer's disease: a differential diagnosis from idiopathic normal pressure hydrocephalus

    Microsoft Academic Search

    Soraya El Sankari; Catherine Gondry-Jouet; Anthony Fichten; Olivier Godefroy; Jean Marie Serot; Hervé Deramond; Marc Etienne Meyer; Olivier Balédent

    2011-01-01

    ABSTRACT: BACKGROUND: Phase-contrast magnetic resonance imaging (PC-MRI) enables quantification of cerebrospinal fluid (CSF) flow and total cerebral blood (tCBF) flow and may be of value for the etiological diagnosis of neurodegenerative diseases. This investigation aimed to study CSF flow and intracerebral vascular flow in patients with Alzheimer's disease (AD) and patients with amnesic mild cognitive impairment (a-MCI) and to compare

  14. Cerebrospinal Fluid Dendritic Cells Infiltrate the Brain Parenchyma and Target the Cervical Lymph Nodes under Neuroinflammatory Conditions

    Microsoft Academic Search

    Eric Hatterer; Monique Touret; Marie-Françoise Belin; Jérôme Honnorat; Serge Nataf; Jean Kanellopoulos

    2008-01-01

    BackgroundIn many neuroinflammatory diseases, dendritic cells (DCs) accumulate in several compartments of the central nervous system (CNS), including the cerebrospinal fluid (CSF). Myeloid DCs invading the inflamed CNS are thus thought to play a major role in the initiation and perpetuation of CNS-targeted autoimmune responses. We previously reported that, in normal rats, DCs injected intra-CSF migrated outside the CNS and

  15. Cerebrospinal fluid adenosine 3',5'-monophosphate, 5-hydroxyindoleacetic acid and homovanillic acid in patients with sleep apnoea syndrome

    PubMed Central

    Cramer, H; Warter, J-M; Renaud, B; Krieger, J; Marescaux, CHR; Hammers, R

    1981-01-01

    Adenosine 3',5'-monophosphate (cyclic AMP), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were determined in the cerebrospinal fluid of patients with respiratory disorder and hypersomnia and in control patients. Patients with the sleep apnoea syndrome confirmed polygraphically showed elevated levels of cyclic AMP and 5-HIAA. Cyclic AMP levels were inversely correlated with arterial Po2, measured under resting conditions. The level of HVA also was raised, but the change was not statistically significant. PMID:6174700

  16. Cerebrospinal fluid and serum concentrations of the N-methyl- d-aspartate (NMDA) receptor antagonist memantine in man

    Microsoft Academic Search

    J. Kornhuber; G. Quack

    1995-01-01

    Memantine is a uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist with therapeutic potential in dementia, spasticity and Parkinson's disease. The Ki-value of memantine at the phencyclidine (PCP) binding site of the NMDA receptor is 0.5 ?M in human frontal cortex. We investigated whether concentrations of mementine in cerebrospinal fluid (CSF) and serum samples under therapeutic conditions are in the range of its

  17. Cerebrospinal Fluid from Subarachnoid Haemorrhage Patients Causes Excessive Oxidative Metabolism Compared to Vascular Smooth Muscle Force Generation

    Microsoft Academic Search

    G. J. Pyne; T. A. D. Cadoux-Hudson; J. F. Clark

    2001-01-01

    Summary  ?Cerebrospinal fluid (CSF) from subarachnoid haemorrhage (SAH) patients can stimulate vascular smooth muscle to generate force\\u000a in vitro. CSF from SAH patients suffering from delayed ischaemic neurological deficits due to cerebral vasospasm can generate\\u000a near maximal force in vitro and previous experiments have ascribed this generation of force to be a calcium mediated event.\\u000a The intracellular calcium concentration has been

  18. IgM quantification in the cerebrospinal fluid of sleeping sickness patients by a latex card agglutination test

    Microsoft Academic Search

    V. Lejon; D. Legros; M. Richer; J. A. Ruiz; V. Jamonneau; P. Truc; F. Doua; N. Dje; F. X. N'Siesi; S. Bisser; E. Magnus; I. Wouters; J. Konings; T. Vervoort; F. Sultan; P. Buscher

    2002-01-01

    Summary An increased IgM concentration in cerebrospinal fluid (CSF), occurring as a consequence of massive intrathecal IgM synthesis, is a marker of interest for diagnosis of the meningo-encephalitic stage in human African trypanosomiasis. However, in current practice, IgM in CSF is not determined because of the lack of a simple and robust test that is applicable in African rural regions

  19. Intrathecal 4-Hydroperoxycyclophosphamide: Neurotoxicity, Cerebrospinal Fluid Pharmacokinetics, and Antitumor Activity in a Rabbit Model of VX2 Leptomeningeal Carcinomatosisl

    Microsoft Academic Search

    Peter C. Phillips; Thuy T. Than; Linda C. Cork; John Hilton; Benjamin S. Carson; O. Michael Colvin; Louise B. Grochow

    Dissemination of tumor to the leptomeninges and cerebrospinal fluid represents a common pattern of metastasis for many cancers; however, few chemotherapeutic agents are available for intrathecal (i.t.) use and treatment results are often poor. We studied the neurotoxicity and phar- macokinetics of i.t. 4-hydroperoxycyclophosphamide (4-HC) in the rab bit and the activity of i.t. 4-HC in a VX2 rabbit model

  20. Clonally expanded plasma cells in the cerebrospinal fluid of patients with central nervous system autoimmune demyelination produce “oligoclonal bands”

    Microsoft Academic Search

    Hans-Christian von Büdingen; Monica Gulati; Sandra Kuenzle; Katja Fischer; Tobias A. Rupprecht; Norbert Goebels

    2010-01-01

    Clonally expanded plasma cells (cePC) and oligoclonal IgG (oligoclonal bands, OCB) in the cerebrospinal fluid (CSF) suggest an involvement of B cell mechanisms in autoimmune CNS demyelination. Due to their CSF-restricted occurrence, OCB are commonly believed to be the products of B cells inside the borders of the blood brain barrier. A comparison of CSF cell Ig transcriptomes and CSF-Ig

  1. Effects of mild hypothermia therapy on the levels of glutathione in rabbit blood and cerebrospinal fluid after cardiopulmonary resuscitation

    PubMed Central

    Zhao, Hui; Chen, Yueliang

    2015-01-01

    Objective(s): The aim of this study was to investigate the effects of mild hypothermia therapy on oxidative stress injury of rabbit brain tissue after cardiopulmonary resuscitation (CPR). Materials and Methods: Rabbit models of cardiac arrest were established. After the restoration of spontaneous circulation, 50 rabbits were randomly divided into normothermia and hypothermia groups. The following five time points were selected: before CPR, immediately after CPR, 2 hr after CPR (hypothermia group reached the target temperature), 14 hr after CPR (hypothermia group before rewarming), and 24 hr after CPR (hypothermia group recovered to normal temperature). Glutathione (GSH) concentrations in both the blood and cerebrospinal fluid of the normothermia and hypothermia groups were measured. Results: At 2, 14, and 24 hr after CPR, the GSH concentrations in both the blood and cerebrospinal fluid were significantly higher in the hypothermia group than in the nomorthermia group. Conclusion: Mild hypothermia therapy may increase GSH concentrations in rabbit blood and cerebrospinal fluid after CPR as well as promote the recovery of cerebral function. PMID:25810895

  2. Viral antibodies in cerebrospinal fluid of multiple sclerosis and control patients: comparison between radioimmunoassay and conventional techniques.

    PubMed Central

    Forghani, B; Cremer, N E; Johnson, K P; Ginsberg, A H; Likosky, W H

    1978-01-01

    Cerebrospinal fluid antibodies to measles, rubella, vaccinia, herpes simplex, and varicella-zoster viruses in four patient study groups (clinically definite multiple sclerosis [MS], early probable MS, optic neuritis, and control patients with other neurological diseases) were assayed by radioimmunoassay, complement fixation, hemagglutination-inhibition, or complement-enhanced plaque reduction methods. Antibodies were more frequently found and at higher dilutions by radioimmunoassay than by other techniques. Measles virus antibody, the most frequently found antibody, was present in the cerebrospinal fluid of 72% of MS patients and 5% of control patients. The differences between the numbers of MS patients and control patients with antibodies to other viruses were not as marked. Thus, 58% of MS patients versus 21% of control patients had antibody to rubella virus, 20 versus 3% had antibody to vaccinia virus, 50 versus 33% had antibody to herpes simplex virus, and 25 versus 8% had antibody to varicella virus. Sixty-seven percent of MS patients and 26% of control patients had antibodies to two or more viruses in their cerebrospinal fluid. PMID:203605

  3. Management of meningitis due to antibiotic-resistant Acinetobacter species.

    PubMed

    Kim, Baek-Nam; Peleg, Anton Y; Lodise, Thomas P; Lipman, Jeffrey; Li, Jian; Nation, Roger; Paterson, David L

    2009-04-01

    Acinetobacter meningitis is becoming an increasingly common clinical entity, especially in the postneurosurgical setting, with mortality from this infection exceeding 15%. Infectious Diseases Society of America guidelines for therapy of postneurosurgical meningitis recommend either ceftazidime or cefepime as empirical coverage against Gram-negative pathogens. However, assessment of the pharmacodynamics of these cephalosporins in cerebrospinal fluid suggests that recommended doses will achieve pharmacodynamic targets against fewer than 10% of contemporary acinetobacter isolates. Thus, these antibiotics are poor options for suspected acinetobacter meningitis. From in vitro and pharmacodynamic perspectives, intravenous meropenem plus intraventricular administration of an aminoglycoside may represent a superior, albeit imperfect, regimen for suspected acinetobacter meningitis. For cases of meningitis due to carbapenem-resistant acinetobacter, use of tigecycline is not recommended on pharmacodynamic grounds. The greatest clinical experience rests with use of polymyxins, although an intravenous polymyxin alone is inadvisable. Combination with an intraventricularly administered antibiotic plus removal of infected neurosurgical hardware appears the therapeutic strategy most likely to succeed in this situation. Unfortunately, limited development of new antibiotics plus the growing threat of multidrug-resistant acinetobacter is likely to increase the problems posed by acinetobacter meningitis in the future. PMID:19324297

  4. Measurement of fluorescent probes concentration ratio in the cerebrospinal fluid for early detection of Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Harbater, Osnat; Gannot, Israel

    2014-03-01

    The pathogenic process of Alzheimer's Disease (AD), characterized by amyloid plaques and neurofibrillary tangles in the brain, begins years before the clinical diagnosis. Here, we suggest a novel method which may detect AD up to nine years earlier than current exams, minimally invasive, with minimal risk, pain and side effects. The method is based on previous reports which relate the concentrations of biomarkers in the Cerebrospinal Fluid (CSF) (A? and Tau proteins) to the future development of AD in mild cognitive impairment patients. Our method, which uses fluorescence measurements of the relative concentrations of the CSF biomarkers, replaces the lumbar puncture process required for CSF drawing. The process uses a miniature needle coupled trough an optical fiber to a laser source and a detector. The laser radiation excites fluorescent probes which were prior injected and bond to the CSF biomarkers. Using the ratio between the fluorescence intensities emitted from the two biomarkers, which is correlated to their concentration ratio, the patient's risk of developing AD is estimated. A theoretical model was developed and validated using Monte Carlo simulations, demonstrating the relation between fluorescence emission and biomarker concentration. The method was tested using multi-layered tissue phantoms simulating the epidural fat, the CSF in the sub-arachnoid space and the bone. These phantoms were prepared with different scattering and absorption coefficients, thicknesses and fluorescence concentrations in order to simulate variations in human anatomy and in the needle location. The theoretical and in-vitro results are compared and the method's accuracy is discussed.

  5. The association between acetaminophen concentrations in the cerebrospinal fluid and temperature decline in febrile infants.

    PubMed

    Kozer, Eran; Hahn, Yuval; Berkovitch, Matitiahu; Chaim, Adina Bar; Brandriss, Norit; Verjee, Zul; Mor, Anat; Goldman, Michael

    2007-12-01

    The objective of this study consisting of a prospective cohort of febrile infants was to describe the correlation between cerebrospinal fluid (CSF) acetaminophen (paracetamol) concentrations and changes in body temperature in febrile infants. Infants, one week to one year of age, with rectal temperature >or=38.0 degrees C, treated with acetaminophen were studied if they underwent a lumbar puncture (LP). Patients received 15 mg/kg of acetaminophen 30 minutes to 4 hours before lumbar puncture was performed. Rectal temperature was documented before acetaminophen administration and at the time of lumbar puncture. Plasma and CSF acetaminophen levels were determined using high-pressure liquid chromatography. Thirty-one infants were studied. In a nonlinear regression, the relationship among acetaminophen concentrations in the CSF, time, and temperature differences is best described by a Lorentzian distribution. The model suggests that a peak effect on temperature is achieved at CSF concentration of 11.9 microg/mL and 182 minutes after acetaminophen administration (P<0.001 and P<0.001, respectively r=0.9 adjusted r square=0.78). Temperature decrement in young febrile infants, treated with acetaminophen, correlates with time and acetaminophen concentrations in the CSF. High concentrations of acetaminophen in the CSF, exceeding a certain level, are not associated with greater temperature decrement. PMID:18043482

  6. Serological tests in cerebrospinal fluid for congenital syphilis in central Africa.

    PubMed

    Gendrel, D; Mefane, C; Nardou, M; Moreno, J L; Engohan, E; Moussavou, A; Nguemby-Mbina, C

    1992-01-01

    Serological tests were performed in the cerebrospinal fluid (CSF) of 13 children with active congenital syphilis (presence of specific IgM FTA-ABS antibodies) and of seven seropositive children with no active syphilis (FTA-ABS IgM-negative) born to syphilitic treated mothers in Libreville, Gabon. Antibodies against treponema were measured by the Venereal Disease Research Laboratory test (VDRL), the Treponema pallidum haemagglutination assay (TPHA) and the fluorescent treponema antibody absorption tests (FTA-ABS IgG and IgM). Of the 13 children with active syphilis, seven had a positive FTA-ABS IgG in the CSF. The result of this test was not correlated with the severity of clinical features, CSF protein levels or number of CSF white blood cells. The CSF-TPHA test was positive in four out of 12 children, and the CSF-VDRL test was negative in all the children with active congenital syphilis. One of the seven newborns with mother-transmitted antibodies had a positive FTA-ABS and TPHA in the CSF. These data show that the VDRL is not sensitive enough to diagnose congenital neurosyphilis, and that FTA-ABS or, at least, TPHA are convenient, sometimes with false-positive results, when a sophisticated method of detecting specific IgM in CSF is not available. PMID:1280042

  7. NMR metabonomics of cerebrospinal fluid distinguishes between Parkinson's disease and controls.

    PubMed

    Öhman, Anders; Forsgren, Lars

    2015-05-01

    This study assesses if nuclear magnetic resonance (NMR) metabonomics can discriminate between Parkinson's disease (PD) patients and control subjects, and consequently identify metabolic markers for the disease. One-dimensional (1)H NMR spectroscopy was used for quantitative analysis of metabolites in the cerebrospinal fluid (CSF) from 10 PD patients and 10 control individuals, together with uni- and multivariate statistical analysis to discriminate between the groups and to identify significantly altered metabolite concentrations. In total 60 metabolites were identified and of those 38 were quantified in all CSF samples. An overall lowering of metabolite content was observed in PD patients compared to control subjects (fold change of 0.85±0.30). Multivariate statistics reveal significant changes (?w*?>0.2) among nine metabolites (alanine, creatinine, dimethylamine, glucose, lactate, mannose, phenylalanine, 3-hydroxyisobutyric acid and 3-hydroxyisovaleric acid). Three of these (alanine, creatinine and mannose) are identified as significantly changed also by univariate statistics (p<0.00132, Bonferroni corrected). Panels with all or a selected set of these metabolites were successfully used for discriminating between the two groups. In conclusion, NMR metabonomics can readily determine metabolite concentrations in CSF, identify putative biomarkers that distinguish between the PD patients and control subjects, and thus potentially become a tool for diagnostic purposes. PMID:25817365

  8. Technetium Tc-99m pyrophosphate for cerebrospinal fluid leaks: radiopharmaceutical considerations.

    PubMed

    Ponto, James A; Graham, Michael M

    2014-01-01

    OBJECTIVE To confirm the anticipated image quality and absence of adverse reactions in patients undergoing clinical practice cerebrospinal fluid (CSF) leak imaging procedures using technetium Tc-99m pyrophosphate (PYP). METHODS Following the recent discontinuation of preservative-free calcium trisodium diethylene triamine pentaacetic acid kits, PYP was selected as a suitable alternative for CSF leak imaging procedures. Procedures were established for its preparation and dispensing, paying special attention to safety considerations, and its use in clinical practice was implemented. Medical records, including images, were reviewed for the first 15 patients undergoing clinical practice CSF imaging procedures using Tc-99m PYP to confirm anticipated image quality and absence of adverse effects. RESULTS Review of CSF leak imaging procedures using Tc-99m PYP in 15 patients showed images to be of uniformly high quality. The vast majority of injected radiopharmaceutical remained in the CSF throughout the duration of the imaging procedure, allowing visualization of CSF leaks. Only a small amount of Tc-99m PYP diffused into the blood with resultant uptake on the skeleton and excretion into the urine, which did not interfere with image interpretation. No adverse reactions were noted in any of the patients. CONCLUSION With proper attention to safety considerations, Tc-99m PYP is a safe and effective alternative for performing CSF leak imaging procedures. PMID:24257695

  9. Total tau is increased, but phosphorylated tau not decreased, in cerebrospinal fluid in amyotrophic lateral sclerosis.

    PubMed

    Wilke, Carlo; Deuschle, Christian; Rattay, Tim W; Maetzler, Walter; Synofzik, Matthis

    2015-02-01

    In amyotrophic lateral sclerosis (ALS), objective biomarkers are needed for early diagnosis and progression monitoring. Reduced phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) has recently been proposed to provide such a biomarker in ALS. Here, we aimed to scrutinize this notion, evaluating both p-tau and total tau (t-tau) in CSF of ALS patients and control subjects. CSF p-tau and t-tau levels were measured in 60 consecutive ALS patients and 120 control subjects without neurodegenerative disease, using an established specific enzyme-linked immunosorbent assay method. Contrary to recent reports, CSF p-tau was not significantly reduced in ALS patients compared with control subjects (p = 0.287). However, CSF t-tau was significantly increased (p < 0.001). Correspondingly, the ratio of p-tau to t-tau was significantly reduced in ALS (p < 0.001). The area under the curve demonstrated poor sensitivity and specificity for p-tau, but moderate sensitivity and specificity for t-tau and p-tau/t-tau ratio. Thus, CSF p-tau by itself does not appear a suitable diagnostic biomarker for ALS, whereas CSF t-tau is a (probably unspecific) marker of the neuronal degeneration in ALS. PMID:25453560

  10. Volume transmission of beta-endorphin via the cerebrospinal fluid; a review

    PubMed Central

    2012-01-01

    There is increasing evidence that non-synaptic communication by volume transmission in the flowing CSF plays an important role in neural mechanisms, especially for extending the duration of behavioral effects. In the present review, we explore the mechanisms involved in the behavioral and physiological effects of ?-endorphin (?-END), especially those involving the cerebrospinal fluid (CSF), as a message transport system to reach distant brain areas. The major source of ?-END are the pro-opio-melano-cortin (POMC) neurons, located in the arcuate hypothalamic nucleus (ARH), bordering the 3rd ventricle. In addition, numerous varicose ?-END-immunoreactive fibers are situated close to the ventricular surfaces. In the present paper we surveyed the evidence that volume transmission via the CSF can be considered as an option for messages to reach remote brain areas. Some of the points discussed in the present review are: release mechanisms of ?-END, independence of peripheral versus central levels, central ?-END migration over considerable distances, behavioral effects of ?-END depend on location of ventricular administration, and abundance of mu and delta opioid receptors in the periventricular regions of the brain. PMID:22883598

  11. HIV migration between blood and cerebrospinal fluid or semen over time.

    PubMed

    Chaillon, Antoine; Gianella, Sara; Wertheim, Joel O; Richman, Douglas D; Mehta, Sanjay R; Smith, David M

    2014-05-15

    Previous studies reported associations between neuropathogenesis and human immunodeficiency virus (HIV) compartmentalization in cerebrospinal fluid (CSF) and between sexual transmission and human immunodeficiency virus type 1 (HIV) compartmentalization in semen. It remains unclear, however, how compartmentalization dynamics change over time. To address this, we used statistical methods and Bayesian phylogenetic approaches to reconstruct temporal dynamics of HIV migration between blood and CSF and between blood and the male genital tract. We investigated 11 HIV-infected individuals with paired semen and blood samples and 4 individuals with paired CSF and blood samples. Aligned partial HIV env sequences were analyzed by (1) phylogenetic reconstruction, using a Bayesian Markov-chain Monte Carlo approach; (2) evaluation of viral compartmentalization, using tree-based and distance-based methods; and (3) analysis of migration events, using a discrete Bayesian asymmetric phylogeographic approach of diffusion with Markov jump counts estimation. Finally, we evaluated potential correlates of viral gene flow across anatomical compartments. We observed bidirectional replenishment of viral compartments and asynchronous peaks of viral migration from and to blood over time, suggesting that disruption of viral compartment is transient and directionally selected. These findings imply that viral subpopulations in anatomical sites are an active part of the whole viral population and that compartmental reservoirs could have implications in future eradication studies. PMID:24302756

  12. Neuronal and Glia-Related Biomarkers in Cerebrospinal Fluid of Patients with Acute Ischemic Stroke

    PubMed Central

    Hjalmarsson, Clara; Bjerke, Maria; Andersson, Björn; Blennow, Kaj; Zetterberg, Henrik; Åberg, N David; Olsson, Bob; Eckerström, Carl; Bokemark, Lena; Wallin, Anders

    2014-01-01

    BACKGROUND Cerebral ischemia promotes morphological reactions of the neurons, astrocytes, oligodendrocytes, and microglia in experimental studies. Our aim was to examine the profile of CSF (cerebrospinal fluid) biomarkers and their relation to stroke severity and degree of white matter lesions (WML). METHODS A total of 20 patients (mean age 76 years) were included within 5–10 days after acute ischemic stroke (AIS) onset. Stroke severity was assessed using NIHSS (National Institute of Health stroke scale). The age-related white matter changes (ARWMC) scale was used to evaluate the extent of WML on CT-scans. The concentrations of specific CSF biomarkers were analyzed. RESULTS Patients with AIS had significantly higher levels of NFL (neurofilament, light), T-tau, myelin basic protein (MBP), YKL-40, and glial fibrillary acidic protein (GFAP) compared with controls; T-Tau, MBP, GFAP, and YKL-40 correlated with clinical stroke severity, whereas NFL correlated with severity of WML (tested by Mann–Whitney test). CONCLUSIONS Several CSF biomarkers increase in AIS, and they correlate to clinical stroke severity. However, only NFL was found to be a marker of degree of WML. PMID:24932109

  13. Leptin Levels Are Negatively Correlated with 2-Arachidonoylglycerol in the Cerebrospinal Fluid of Patients with Osteoarthritis

    PubMed Central

    Nicholson, James; Azim, Syed; Rebecchi, Mario J.; Galbavy, William; Feng, Tian; Reinsel, Ruth; Rizwan, Sabeen; Fowler, Christopher J.; Benveniste, Helene; Kaczocha, Martin

    2015-01-01

    Background There is compelling evidence in humans that peripheral endocannabinoid signaling is disrupted in obesity. However, little is known about the corresponding central signaling. Here, we have investigated the relationship between gender, leptin, body mass index (BMI) and levels of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in the serum and cerebrospinal fluid (CSF) of primarily overweight to obese patients with osteoarthritis. Methodology/Principal Findings Patients (20 females, 15 males, age range 44-78 years, BMI range 24-42) undergoing total knee arthroplasty for end-stage osteoarthritis were recruited for the study. Endocannabinoids were quantified by liquid chromatography – mass spectrometry. AEA and 2-AG levels in the serum and CSF did not correlate with either age or BMI. However, 2-AG levels in the CSF, but not serum, correlated negatively with CSF leptin levels (Spearman’s ? -0.48, P=0.0076, n=30). No such correlations were observed for AEA and leptin. Conclusions/Significance In the patient sample investigated, there is a negative association between 2-AG and leptin levels in the CSF. This is consistent with pre-clinical studies in animals, demonstrating that leptin controls the levels of hypothalamic endocannabinoids that regulate feeding behavior. PMID:25835291

  14. Analysis of cerebrospinal fluid ?-aminobutyric acid by capillary electrophoresis with laser-induced fluorescence detection.

    PubMed

    Casado, Mercedes; Molero, Marta; Sierra, Cristina; García-Cazorla, Angels; Ormazabal, Aida; Artuch, Rafael

    2014-04-01

    The measurement of ?-aminobutyric acid (GABA) is suitable for investigating various neurological disorders. In this study, a sensitive and selective method for free GABA quantification in cerebrospinal fluid (CSF) has been standardised. This method is based on CE with LIF detection using 4-fluoro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-F) as a derivatisating agent. The reaction conditions (NBD-F concentration, pH, temperature and reaction time) and the electrophoretic parameters (run buffer composition and pH and separation voltage) were optimised to obtain the maximum derivatisation efficiency and electrophoretic resolution. The best resolution was obtained using 200 mM sodium borate, 10 mM SDS, 8.5 mM ?-CD, pH 10 and 20 kV voltage. The method was linear in the concentration range of 2.5-1000 nM with good inter- and intra-assay precision values. The effects of CSF handling on free GABA concentrations were also evaluated. Our results show that the time delay between CSF collection and freezing strongly increases the CSF GABA values. Age-related reference values were established in 55 paediatric controls. The influence of antiepileptic therapy on free CSF GABA was studied in 38 neuropaediatric patients. Significantly, higher GABA values were obtained in patients taking valproic acid or vigabatrin therapy, which are antiepileptic drugs that modulate GABA metabolism. PMID:24338894

  15. Measurement of cerebrospinal fluid formation and absorption by ventriculo-cisternal perfusion: what is really measured?

    PubMed Central

    Oreškovi?, Darko; Klarica, Marijan

    2014-01-01

    The generally accepted hypothesis on cerebrospinal fluid (CSF) hydrodynamics suggests that CSF is actively formed mainly by choroid plexuses, circulates unidirectionally along the brain ventricles and subarachnoid space, and is passively absorbed mainly into the dural venous sinuses. CSF formation rate (Vf) has been extensively studied using the ventriculo-cisternal perfusion technique and the results have been used as the key evidence confirming the mentioned hypothesis. This method and the equation for Vf calculation are based on the assumption that the dilution of the indicator substance is a consequence of the newly formed CSF, ie, that a higher CSF formation rate will result in a higher degree of dilution. However, it has been experimentally shown that the indicator substance dilution inside the CSF system does not occur because of a “newly formed” CSF, but as consequence of a number of other factors (departure of substances into the surrounding tissue, flowing around the collecting cannula into the cortical and spinal subarachnoid space, departure into the contralateral ventricle, etc). This technique allows “calculation” of the CSF formation even in dead animals, in an in vitro model, and in any other part of the CSF system outside the ventricles that is being perfused. Therefore, this method is indirect and any dilution of the indicator substance in the perfusate caused by other reasons would result in questionable and often contradictory conclusions regarding CSF formation rates. PMID:25165046

  16. Tau in cerebrospinal fluid: a sensitive sandwich enzyme-linked immunosorbent assay using tyramide signal amplification

    PubMed Central

    Yamamori, Hidenaga; Khatoon, Sabiha; Grundke-Iqbal, Inge; Blennow, Kaj; Ewers, Michael; Hampel, Harald; Iqbal, Khalid

    2007-01-01

    Tau in cerebrospinal fluid (CSF) has been proposed as a diagnostic marker for Alzheimer’s disease (AD). This paper presents a new sensitive sandwich ELISA allowing quantitation of tau from 8 ?l CSF/well. A human specific monoclonal tau antibody HT7 was used as a capture antibody and a mixture of polyclonal tau antibodies, 92e and R134d was used as reporter antibodies. Tyramide signal amplification (TSA) technology was used in the last step to increase the sensitivity. With this TSA-ELISA, the lowest detection limit for tau was 14.3 pg/ml. Tau levels in CSF were found to be increased in AD patients (807 ± 304 pg/ml, p< 0.001) compared with controls (252 ± 94 pg/ml). Thirty-five of 38 AD cases (92% sensitivity) yielded signals greater than cutoff, while only 1 of 38 control cases (97% specificity) was greater. A highly significant correlation was found between this assay and a commonly used kit, INNOTEST hTAU Antigen. PMID:17400380

  17. Targeted human cerebrospinal fluid proteomics for the validation of multiple Alzheimer’s disease biomarker candidates

    PubMed Central

    Choi, Yong Seok; Hou, Shuyu; Choe, Leila H.; Lee, Kelvin H.

    2013-01-01

    There is significant interest in the development of methods to validate novel biomarkers for Alzheimer’s disease (AD) diagnosis. Previously, a proteomic panel of cerebrospinal fluid (CSF) biomarker candidates that differentiated AD and non-AD CSF with accuracy higher than 90% was found; information about these CSF proteins can be used to develop multiple reaction monitoring (MRM) based analytical assays, which offer the possibility of quantifying protein expression level changes in samples, as well as, validation among multiple laboratories. Here we report an MRM assay that demonstrates good linearity (average R2 = 0.969) and reproducibility (average coefficient of variance of 6.93%) for the proposed AD CSF biomarkers. MRM quantification results of A?1-40, A?1-42, retinol-binding protein and cystatin C correlated well with those from ELISA (average R2 = 0.974). Analysis shows that 12 out of 16 selected targets exhibit the same trend in protein expression as that in literature. PMID:23735279

  18. Cytokines in the cerebrospinal fluids of patients with chronic fatigue syndrome/myalgic encephalomyelitis.

    PubMed

    Peterson, D; Brenu, E W; Gottschalk, G; Ramos, S; Nguyen, T; Staines, D; Marshall-Gradisnik, S

    2015-01-01

    Objectives. Previous research has provided evidence for dysregulation in peripheral cytokines in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). To date only one study has examined cytokines in cerebrospinal fluid (CSF) samples of CFS/ME patients. The purpose of this pilot study was to examine the role of cytokines in CSF of CFS/ME patients. Methods. CSF was collected from 18 CFS/ME patients and 5 healthy controls. The CSF samples were examined for the expression of 27 cytokines (interleukin- (IL-) 1?, IL-1ra, IL-2, IL-4, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17, basic FGF, eotaxin, G-CSF, GM-CSF, IFN-?, IP-10, MCP-1 (MCAF), MIP-1?, MIP-1?, PDGF-BB, RANTES, TNF-?, and VEGF) using the Bio-Plex Human Cytokine 27-plex Assay. Results. Of the 27 cytokines examined, only IL-10 was significantly reduced in the CFS/ME patients in comparison to the controls. Conclusions. This preliminary investigation suggests that perturbations in inflammatory cytokines in the CSF of CFS/ME patients may contribute to the neurological discrepancies observed in CFS/ME. PMID:25834308

  19. Enhanced detection of CNS cell secretome in plasma protein-depleted cerebrospinal fluid.

    PubMed

    Thouvenot, Eric; Urbach, Serge; Dantec, Christelle; Poncet, Joël; Séveno, Martial; Demettre, Edith; Jouin, Patrick; Touchon, Jacques; Bockaert, Joël; Marin, Philippe

    2008-10-01

    Human cerebrospinal fluid (CSF) proteome is actively investigated to identify relevant biomarkers and therapeutic targets for neurological disorders. Approximately 80% of CSF proteome originate from plasma, yielding a high dynamic range in CSF protein concentration and precluding identification of potential biomarkers originating from CNS cells. Here, we have adapted the most complete multiaffinity depletion method available to remove 20 abundant plasma proteins from a CSF pool originating from patients with various cognitive disorders. We identified 622 unique CSF proteins in immunodepleted plus retained fractions versus 299 in native CSF, including 22 proteins hitherto not identified in CSF. Parallel analysis of neuronal secretome identified 34 major proteins secreted by cultured cortical neurons (cell adhesion molecules, proteins involved in neurite outgrowth and axonal guidance, modulators of synaptic transmission, proteases and protease inhibitors) of which 76% were detected with a high confidence in immunodepleted CSF versus 50% in native CSF. Moreover, a majority of proteins previously identified as secretory products of choroid plexus cells or astrocytes were detected in immunodepleted CSF. Hence, removal of 20 major plasma proteins from CSF improves detection of brain cell-derived proteins in CSF and should facilitate identification of relevant biomarkers in CSF proteome profiling analyses. PMID:18774838

  20. Flowing cerebrospinal fluid in normal and hydrocephalic states: Appearance on MR images

    SciTech Connect

    Bradley, W.G.; Kortman, K.E.; Burgoyne, B.; Eng, D.

    1986-06-01

    The signal intensity of the cerebrospinal fluid (CSF) in the cerebral aqueduct and lateral ventricles on magnetic resonance (MR) images was evaluated in 16 healthy individuals and in 32 patients with various forms of hydrocephalus (20 with chronic normal pressure hydrocephalus (NPH), seven with acute communicating hydrocephalus, and five with hydrocephalus ex vacuo (atrophy)). The low signal intensity frequently observed in the cerebral aqueduct is believed to reflect the pulsatile motion of CSF, which is related to the cardiac cycle. While this aqueductal flow void phenomenon can be observed in healthy individuals, it is most pronounced in patients with chronic, communicating NPH; is less evident in patients with acute, communicating hydrocephalus and is least evident in patients with atrophy. Ventricular compliance is known to be essentially normal in atrophy, mildly decreased in acute, communicating hydrocephalus; and severely decreased in NPH. The degree of aqueductal signal loss is believed to reflect the velocity of the pulsatile CSF motion, which in turn depends on the relative ventricular compliance and surface area.

  1. Natural killer cell subsets in cerebrospinal fluid of patients with multiple sclerosis.

    PubMed

    Rodríguez-Martín, E; Picón, C; Costa-Frossard, L; Alenda, R; Sainz de la Maza, S; Roldán, E; Espiño, M; Villar, L M; Álvarez-Cermeño, J C

    2015-05-01

    Changes in blood natural killer (NK) cells, important players of the immune innate system, have been described in multiple sclerosis (MS). We studied percentages and total cell counts of different effector and regulatory NK cells in cerebrospinal fluid (CSF) of MS patients and other neurological diseases to gain clearer knowledge of the role of these cells in neuroinflammation. NK cell subsets were assessed by flow cytometry in CSF of 85 consecutive MS patients (33 with active disease and 52 with stable MS), 16 with other inflammatory diseases of the central nervous system (IND) and 17 with non-inflammatory neurological diseases (NIND). MS patients showed a decrease in percentages of different CSF NK subpopulations compared to the NIND group. However, absolute cell counts showed a significant increase of all NK subsets in MS and IND patients, revealing that the decrease in percentages does not reflect a real reduction of these immune cells. Remarkably, MS patients showed a significant increase of regulatory/effector (CD56(bright) /CD56(dim) ) NK ratio compared to IND and NIND groups. In addition, MS activity associated with an expansion of NK?T cells. These data show that NK cell subsets do not increase uniformly in all inflammatory neurological disease and suggest strongly that regulatory CD56(bright) and NK?T cells may arise in CSF of MS patients as an attempt to counteract the CNS immune activation characteristic of the disease. PMID:25565222

  2. Analysis of cerebrospinal fluid for detection of ruptured cerebral aneurysm using spectrophotometry and signal processing techniques

    NASA Astrophysics Data System (ADS)

    Majumder, Anindya; Caffery, James, Jr.; Bhadri, Prashant R.; Beyette, Fred R., Jr.; Clark, Joseph F.; Morgan, Chad J.; Pyne, Gail J.; Zuccarello, Mario; Jauch, Ed; Wagner, Ken R.

    2004-07-01

    An accurate quantification of bilirubin in cerebrospinal fluid (CSF) will provide a simple, sensitive and rapid mechanism for detecting subarachnoid hemorrhage (SAH) and for its differentiation from a traumatic spinal tap. Derivative analysis of the spectrophotometric data provides a model for determining bilirubin in CSF where the primary contaminant is Methemoglobin. Bilirubin values are determined in the range 0-9mg/dl within a methemoglobin concentration of 4.6g/dl using the derivative analysis method. The algorithm is also implemented on test samples in which the bilirubin value is constant (4.6mg/dl) and the methemoglobin varies between 0-9g/dl. The performance of the derivative analysis method is compared to the modified minimum distance method developed in reference one. We suggest a combination of these methods for accurate bilirubin estimation in CSF/hemoglobin. This will provide the foundation for the development of a portable user friendly device for diagnosis of SAH.

  3. Cerebrospinal Fluid Metabolome in Mood Disorders-Remission State has a Unique Metabolic Profile

    PubMed Central

    Kaddurah-Daouk, Rima; Yuan, Peixiong; Boyle, Stephen H.; Matson, Wayne; Wang, Zhi; Zeng, Zhao Bang; Zhu, Hongjie; Dougherty, George G.; Yao, Jeffrey K.; Chen, Guang; Guitart, Xavier; Carlson, Paul J.; Neumeister, Alexander; Zarate, Carlos; Krishnan, Ranga R.; Manji, Husseini K.; Drevets, Wayne

    2012-01-01

    Targeted metabolomics provides an approach to quantify metabolites involved in specific molecular pathways. We applied an electrochemistry-based, targeted metabolomics platform to define changes in tryptophan, tyrosine, purine and related pathways in the depressed and remitted phases of major depressive disorder (MDD). Biochemical profiles in the cerebrospinal fluid of unmedicated depressed (n = 14; dMDD) or remitted MDD subjects (n = 14; rMDD) were compared against those in healthy controls (n = 18; HC). The rMDD group showed differences in tryptophan and tyrosine metabolism relative to the other groups. The rMDD group also had higher methionine levels and larger methionine-to-glutathione ratios than the other groups, implicating methylation and oxidative stress pathways. The dMDD sample showed nonsignificant differences in the same direction in several of the metabolic branches assessed. The reductions in metabolites associated with tryptophan and tyrosine pathways in rMDD may relate to the vulnerability this population shows for developing depressive symptoms under tryptophan or catecholamine depletion. PMID:22993692

  4. Passage of delta sleep-inducing peptide (DSIP) across the blood-cerebrospinal fluid barrier

    SciTech Connect

    Zlokovic, B.V.; Segal, M.B.; Davson, H.; Jankov, R.M.

    1988-05-01

    Unidirectional flux of /sup 125/I-labeled DSIP at the blood-tissue interface of the blood-cerebrospinal fluid (CSF) barrier was studied in the perfused in situ choroid plexuses of the lateral ventricles of the sheep. Arterio-venous loss of /sup 125/I-radioactivity suggested a low-to-moderate permeability of the choroid epithelium to the intact peptide from the blood side. A saturable mechanism with Michaelis-Menten type kinetics with high affinity and very low capacity (approximate values: Kt = 5.0 +/- 0.4 nM; Vmax = 272 +/- 10 fmol.min-1) was demonstrated at the blood-tissue interface of the choroid plexus. The clearance of DSIP from the ventricles during ventriculo-cisternal perfusion in the rabbit indicated no significant flux of the intact peptide out of the CSF. The results suggest that DSIP crosses the blood-CSF barrier, while the system lacks the specific mechanisms for removal from the CSF found with most, if not all, amino acids and several peptides.

  5. Effects of blood contamination and the rostro-caudal gradient on the human cerebrospinal fluid proteome.

    PubMed

    Aasebø, Elise; Opsahl, Jill Anette; Bjørlykke, Yngvild; Myhr, Kjell-Morten; Kroksveen, Ann Cathrine; Berven, Frode S

    2014-01-01

    Over the last years there has been an increased focus on the importance of knowing the effect of pre-analytical influence on the proteomes under study, particularly in the field of biomarker discovery. We present three proteomics studies examining the effect of blood contamination and the rostro-caudal gradient (RCG) on the cerebrospinal fluid (CSF) proteome, in addition to plasma/CSF protein ratios. The studies showed that the central nervous system (CNS) derived proteins appeared to be unaffected by the RCG, while the plasma-derived proteins showed an increase in concentration towards the lumbar area. This implies that the concentration of the plasma-derived proteins in CSF will vary depending on the volume of CSF that is collected. In the CSF samples spiked with blood, 262 of 814 quantified proteins showed an abundance increase of more than 1.5 fold, while 403 proteins had a fold change of less than 1.2 and appeared to be unaffected by blood contamination. Proteins with a high plasma/CSF ratio appeared to give the largest effect on the CSF proteome upon blood contamination. The results give important background information on how factors like blood contamination, RCG and blood-CNS-barrier influences the CSF proteome. This information is particularly important in the field of biomarker discovery, but also for routine clinical measurements. The data from the blood contamination and RCG discovery studies have been deposited to the ProteomeXchange with identifier PXD000401. PMID:24599184

  6. Lipidomic analysis of cerebrospinal fluid by mass spectrometry-based methods.

    PubMed

    Colsch, Benoit; Seyer, Alexandre; Boudah, Samia; Junot, Christophe

    2015-01-01

    Lipids are natural substances found in all living organisms. Essential to the integrity of cell membranes, they also have many biological functions linked to energy storage and cell signaling, and are involved in a large number of heterogeneous diseases such as cancer, diabetes, neurological disorders, and inherited metabolic diseases. Lipids are challenging to analyze because of their huge structural diversity and numerous species. Up to now, lipid analysis has been achieved by targeted approaches focusing on selected families and relying on extraction protocols and chromatographic methods coupled to various detectors including mass spectrometry. Thanks to the technological improvements achieved in the fields of chromatography, high-resolution mass spectrometry and bioinformatics, it is possible to perform global lipidomic analyses enabling the concomitant detection, identification and relative quantification of many lipid species belonging to different families. The aim of this review is to focus on mass spectrometry-based methods to perform lipid and lipidomic analyses and on their application to the analysis of cerebrospinal fluid. PMID:25488626

  7. Update on the core and developing cerebrospinal fluid biomarkers for Alzheimer disease

    PubMed Central

    Babi?, Mirjana; Švob Štrac, Dubravka; Mück-Šeler, Dorotea; Pivac, Nela; Stani?, Gabrijela; Hof, Patrick R.; Šimi?, Goran

    2014-01-01

    Alzheimer disease (AD) is a complex neurodegenerative disorder, whose prevalence will dramatically rise by 2050. Despite numerous clinical trials investigating this disease, there is still no effective treatment. Many trials showed negative or inconclusive results, possibly because they recruited only patients with severe disease, who had not undergone disease-modifying therapies in preclinical stages of AD before severe degeneration occurred. Detection of AD in asymptomatic at risk individuals (and a few presymptomatic individuals who carry an autosomal dominant monogenic AD mutation) remains impractical in many of clinical situations and is possible only with reliable biomarkers. In addition to early diagnosis of AD, biomarkers should serve for monitoring disease progression and response to therapy. To date, the most promising biomarkers are cerebrospinal fluid (CSF) and neuroimaging biomarkers. Core CSF biomarkers (amyloid ?1-42, total tau, and phosphorylated tau) showed a high diagnostic accuracy but were still unreliable for preclinical detection of AD. Hence, there is an urgent need for detection and validation of novel CSF biomarkers that would enable early diagnosis of AD in asymptomatic individuals. This article reviews recent research advances on biomarkers for AD, focusing mainly on the CSF biomarkers. In addition to core CSF biomarkers, the potential usefulness of novel CSF biomarkers is discussed. PMID:25165049

  8. The effect of whole body position on lumbar cerebrospinal fluid opening pressure

    PubMed Central

    Sithinamsuwan, Pasiri; Sithinamsuwan, Nakorn; Tejavanija, Sirakarn; Udommongkol, Chesda; Nidhinandana, Samart

    2008-01-01

    We compared cerebrospinal fluid (CSF) opening pressure measurements in the lumbar subarachnoid space between the flexed position (F-OP) and relaxed position (R-OP) in recumbent patients. We devised an equation for using F-OP to determine the existence of raised intracranial pressure (ICP). Patients (n = 83) underwent lumbar puncture while in the flexed lateral decubitus position and then were moved to the relaxed position. F-OP and R-OP were measured with a water manometer. R-OP > 180 mmH2O plus relevant clinical signs were taken as indicators of raised intracranial pressure. Mean pressures for F-OP and R-OP were 178.54 and 160.52 mmH2O respectively, p <0.001. When F-OP > 180, raised ICP could be significantly over diagnosed. The authors recommend an equation [R-OP(calculated, mmH2O) = 0.885 × F-OP(measured, mmH2O)] or using 200 mmH2O as the threshold for increased ICP with flexed posture. PMID:18593481

  9. Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer’s disease

    PubMed Central

    Blennow, Kaj; Dubois, Bruno; Fagan, Anne M.; Lewczuk, Piotr; de Leon, Mony J.; Hampel, Harald

    2015-01-01

    Several potential disease-modifying drugs for Alzheimer’s disease (AD) have failed to show any effect on disease progression in clinical trials, conceivably because the AD subjects are already too advanced to derive clinical benefit from treatment and because diagnosis based on clinical criteria alone introduces a high misdiagnosis rate. Thus, well-validated biomarkers for early detection and accurate diagnosis are crucial. Low cerebrospinal fluid (CSF) concentrations of the amyloid-? (A?1-42) peptide, in combination with high total tau and phosphorylated tau, are sensitive and specific biomarkers highly predictive of progression to AD dementia in patients with mild cognitive impairment. However, interlaboratory variations in the results seen with currently available immunoassays are of concern. Recent worldwide standardization efforts and quality control programs include standard operating procedures for both preanalytical (e.g., lumbar puncture and sample handling) and analytical (e.g., preparation of calibration curve) procedures. Efforts are also ongoing to develop highly reproducible assays on fully automated instruments. These global standardization and harmonization measures will provide the basis for the generalized international application of CSF bio-markers for both clinical trials and routine clinical diagnosis of AD. PMID:24795085

  10. Role of cerebrospinal fluid biomarkers in clinical trials for Alzheimer's disease modifying therapies.

    PubMed

    Kang, Ju-Hee; Ryoo, Na-Young; Shin, Dong Wun; Trojanowski, John Q; Shaw, Leslie M

    2014-12-01

    Until now, a disease-modifying therapy (DMT) that has an ability to slow or arrest Alzheimer's disease (AD) progression has not been developed, and all clinical trials involving AD patients enrolled by clinical assessment alone also have not been successful. Given the growing consensus that the DMT is likely to require treatment initiation well before full-blown dementia emerges, the early detection of AD will provide opportunities to successfully identify new drugs that slow the course of AD pathology. Recent advances in early detection of AD and prediction of progression of the disease using various biomarkers, including cerebrospinal fluid (CSF) A?1-42, total tau and p-tau181 levels, and imagining biomarkers, are now being actively integrated into the designs of AD clinical trials. In terms of therapeutic mechanisms, monitoring these markers may be helpful for go/no-go decision making as well as surrogate markers for disease severity or progression. Furthermore, CSF biomarkers can be used as a tool to enrich patients for clinical trials with prospect of increasing statistical power and reducing costs in drug development. However, the standardization of technical aspects of analysis of these biomarkers is an essential prerequisite to the clinical uses. To accomplish this, global efforts are underway to standardize CSF biomarker measurements and a quality control program supported by the Alzheimer's Association. The current review summarizes therapeutic targets of developing drugs in AD pathophysiology, and provides the most recent advances in the. PMID:25598657

  11. Pathophysiology of increased cerebrospinal fluid pressure associated to brain arteriovenous malformations: The hydraulic hypothesis

    PubMed Central

    Rossitti, Sandro

    2013-01-01

    Background: Brain arteriovenous malformations (AVMs) produce circulatory and functional disturbances in adjacent as well as in remote areas of the brain, but their physiological effect on the cerebrospinal fluid (CSF) pressure is not well known. Methods: The hypothesis of an intrinsic disease mechanism leading to increased CSF pressure in all patients with brain AVM is outlined, based on a theory of hemodynamic control of intracranial pressure that asserts that CSF pressure is a fraction of the systemic arterial pressure as predicted by a two-resistor series circuit hydraulic model. The resistors are the arteriolar resistance (that is regulated by vasomotor tonus), and the venous resistance (which is mechanically passive as a Starling resistor). This theory is discussed and compared with the knowledge accumulated by now on intravasal pressures and CSF pressure measured in patients with brain AVM. Results: The theory provides a basis for understanding the occurrence of pseudotumor cerebri syndrome in patients with nonhemorrhagic brain AVMs, for the occurrence of local mass effect and brain edema bordering unruptured AVMs, and for the development of hydrocephalus in patients with unruptured AVMs. The theory also contributes to a better appreciation of the pathophysiology of dural arteriovenous fistulas, of vein of Galen aneurismal malformation, and of autoregulation-related disorders in AVM patients. Conclusions: The hydraulic hypothesis provides a comprehensive frame to understand brain AVM hemodynamics and its effect on the CSF dynamics. PMID:23607064

  12. A fast and reproducible method for albumin isolation and depletion from serum and cerebrospinal fluid

    PubMed Central

    Holewinski, Ronald J.; Jin, Zhicheng; Powell, Matthew J.; Maust, Matthew D.; Van Eyk, Jennifer E.

    2015-01-01

    Analysis of serum and plasma proteomes is a common approach for biomarker discovery, and the removal of high abundant proteins, such as albumin and immunoglobins, is usually the first step in the analysis of serum and plasma proteomes. However, albumin binds peptides and proteins, which raises concerns as to how the removal of albumin could impact the outcome of the biomarker study while ignoring the possibility that this could be a biomarker sub-proteome itself. The first goal of this study was to test a new commercially available affinity capture reagent from Protea Biosciences and to compare the efficiency and reproducibility to 4 other commercially available albumin depletion methods. The second goal of this study was to determine if there is a highly efficient albumin depletion/isolation system that minimizes sample handling and would be suitable for large numbers of samples. Two of the methods tested (Sigma and ProteaPrep) showed an albumin depletion efficiency of 97% or greater for both serum and cerebrospinal fluid (CSF). Isolated serum and CSF albuminomes from ProteaPrep spin columns were analyzed directly by LC-MS/MS, identifying 128 serum (45 not previously reported) and 94 CSF albuminome proteins (17 unique to the CSF albuminome). Serum albuminome was also isolated using Vivapure anti-HSA columns for comparison, identifying 105 proteins, 81 of which overlapped with the ProteaPrep method. PMID:23300121

  13. Avidity of anti-neurocytoskeletal antibodies in cerebrospinal fluid and serum.

    PubMed

    Fialová, L; Švarcová, J; Bartos, A; Malbohan, I

    2012-09-01

    Antibodies have different avidities that can be evaluated using modified enzyme-linked immunosorbent assay (ELISA) techniques. We determined levels and avidities of antibodies to light (NFL) and medium (NFM) subunits of neurofilaments and tau protein in serum and cerebrospinal fluid (CSF) from 26 patients and anti-tau antibody levels and their avidities in 20 multiple sclerosis (MS) patients and 20 age- and sex-matched controls. Each sample was analyzed using both standard ELISA and also using a similar ELISA protocol with the addition of urea. The avidities of anti-neurocytoskeletal antibodies were higher in the CSF than those in serum (anti-NFL, p < 0.0001; anti-tau, p < 0.01; anti-NFM, n.s.). There was no relationship between avidities in serum and CSF for individual anti-neurocytoskeletal antibodies. We did not observe the relationship among the avidities of various anti-neurocytoskeletal antibodies. The avidities of anti-tau antibodies in the CSF were significantly higher in the MS patients than those in the controls (p < 0.0001). The study demonstrates the differences in avidities of CSF or serum neurocytoskeletal antibodies measured as the urea resistance by ELISA method. Avidity determination of anti-neurocytoskeletal antibodies could contribute to the evaluation of the immunological status of patients. PMID:22566118

  14. Increased Levels of Chitotriosidase and YKL-40 in Cerebrospinal Fluid from Patients with Alzheimer's Disease

    PubMed Central

    Rosén, Christoffer; Andersson, Carl-Henrik; Andreasson, Ulf; Molinuevo, José L.; Bjerke, Maria; Rami, Lorena; Lladó, Albert; Blennow, Kaj; Zetterberg, Henrik

    2014-01-01

    Background The cerebrospinal fluid (CSF) biomarkers total tau, abnormally phosphorylated tau and amyloid ? 1-42 are strongly associated with Alzheimer's disease (AD). Apart from the pathologic hallmarks that these biomarkers represent, other processes such as inflammation and microglial activation are present in the brains of patients with AD. New biomarkers related to these processes could be valuable for the diagnosis and follow-up of AD patients and for the evaluation of inflammation-related pathologies. Aim The aim of this study was to evaluate the association of inflammatory CSF biomarkers with AD. Methods Twenty-five AD patients and 25 controls who had a pathological and normal CSF profile of the core AD biomarkers, respectively, were included in this study. CSF levels of chitotriosidase, YKL-40 (also known as chitinase-3-like protein 1) and monocyte chemoattractant protein-1 (MCP-1) were quantified and the levels compared between the groups. Results AD patients had increased CSF levels of chitotriosidase and YKL-40 (both approximately twice higher than in controls), while the levels of MCP-1 were similar in the AD and control groups. Conclusion The results indicate that chitotriosidase and YKL-40 may be helpful for the evaluation of cerebral inflammatory activity in AD patients. PMID:25254036

  15. The regulation of brain states by neuroactive substances distributed via the cerebrospinal fluid; a review

    PubMed Central

    2010-01-01

    The cerebrospinal fluid (CSF) system provides nutrients to and removes waste products from the brain. Recent findings suggest, however, that in addition, the CSF contains message molecules in the form of actively released neuroactive substances. The concentrations of these vary between locations, suggesting they are important for the changes in brain activity that underlie different brain states, and induce different sensory input and behavioral output relationships. The cranial CSF displays a rapid caudally-directed ventricular flow followed by a slower rostrally-directed subarachnoid flow (mainly towards the cribriform plate and from there into the nasal lymphatics). Thus, many brain areas are exposed to and can be influenced by substances contained in the CSF. In this review we discuss the production and flow of the CSF, including the mechanisms involved in the regulation of its composition. In addition, the available evidence for the release of neuropeptides and other neuroactive substances into the CSF is reviewed, with particular attention to the selective effects of these on distant downstream receptive brain areas. As a conclusion we suggest that (1) the flowing CSF is involved in more than just nutrient and waste control, but is also used as a broadcasting system consisting of coordinated messages to a variety of nearby and distant brain areas; (2) this special form of volume transmission underlies changes in behavioral states. PMID:20157443

  16. Detection of disease-associated ?-synuclein in the cerebrospinal fluid: a feasibility study

    PubMed Central

    Unterberger, Ursula; Lachmann, Ingolf; Voigtländer, Till; Pirker, Walter; Berghoff, Anna S.; Flach, Katharina; Wagner, Uta; Geneste, Aline; Perret-Liaudet, Armand; Kovacs, Gabor G.

    2014-01-01

    With the aim to evaluate the significance and reliability of detecting disease-specific ?-synuclein in the cerebrospinal fluid (CSF) we developed an ELISA and bead-assay. We used a commercial antibody (5G4) that does not bind to the physiological monomeric form of ?-synuclein, but is highly specific for the disease-associated forms, including high molecular weight fraction of ?-sheet rich oligomers. We applied both tests in CSF from a series of neuropathologically confirmed ?-synucleinopathy cases, including Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB) (n = 7), as well as Alzheimer’s disease (n = 6), and control patients without neurodegenerative pathologies (n = 9). Disease-specific ?-synuclein was detectable in the CSF in a subset of patients with ?-synuclein pathology in the brain. When combined with the analysis of total ?-synuclein, the bead-assay for disease-specific ?-synuclein was highly specific for PDD/DLB. Detection of disease-associated ?-synuclein combined with the total levels of ?-synuclein is a promising tool for the in-vivo diagnosis of ?-synucleinopathies, including PDD and LBD. PMID:25131945

  17. Identification of a Biomarker in Cerebrospinal Fluid for Neuronopathic Forms of Gaucher Disease

    PubMed Central

    Zigdon, Hila; Savidor, Alon; Levin, Yishai; Meshcheriakova, Anna; Schiffmann, Raphael; Futerman, Anthony H.

    2015-01-01

    Gaucher disease, a recessive inherited metabolic disorder caused by defects in the gene encoding glucosylceramidase (GlcCerase), can be divided into three subtypes according to the appearance of symptoms associated with central nervous system involvement. We now identify a protein, glycoprotein non-metastatic B (GPNMB), that acts as an authentic marker of brain pathology in neurological forms of Gaucher disease. Using three independent techniques, including quantitative global proteomic analysis of cerebrospinal fluid (CSF) in samples from Gaucher disease patients that display neurological symptoms, we demonstrate a correlation between the severity of symptoms and GPNMB levels. Moreover, GPNMB levels in the CSF correlate with disease severity in a mouse model of Gaucher disease. GPNMB was also elevated in brain samples from patients with type 2 and 3 Gaucher disease. Our data suggest that GPNMB can be used as a marker to quantify neuropathology in Gaucher disease patients and as a marker of treatment efficacy once suitable treatments towards the neurological symptoms of Gaucher disease become available. PMID:25775479

  18. Profiling and identification of cerebrospinal fluid proteins in a rat EAE model of multiple sclerosis.

    PubMed

    Rosenling, Therese; Stoop, Marcel P; Attali, Amos; van Aken, Hans; Suidgeest, Ernst; Christin, Christin; Stingl, Christoph; Suits, Frank; Horvatovich, Peter; Hintzen, Rogier Q; Tuinstra, Tinka; Bischoff, Rainer; Luider, Theo M

    2012-04-01

    The experimental autoimmune encephalomyelitis (EAE) model resembles certain aspects of multiple sclerosis (MScl), with common features such as motor dysfunction, axonal degradation, and infiltration of T-cells. We studied the cerebrospinal fluid (CSF) proteome in the EAE rat model to identify proteomic changes relevant for MScl disease pathology. EAE was induced in male Lewis rats by injection of myelin basic protein (MBP) together with complete Freund's adjuvant (CFA). An inflammatory control group was injected with CFA alone, and a nontreated group served as healthy control. CSF was collected at day 10 and 14 after immunization and analyzed by bottom-up proteomics on Orbitrap LC-MS and QTOF LC-MS platforms in two independent laboratories. By combining results, 44 proteins were discovered to be significantly increased in EAE animals compared to both control groups, 25 of which have not been mentioned in relation to the EAE model before. Lysozyme C1, fetuin B, T-kininogen, serum paraoxonase/arylesterase 1, glutathione peroxidase 3, complement C3, and afamin are among the proteins significantly elevated in this rat EAE model. Two proteins, afamin and complement C3, were validated in an independent sample set using quantitative selected reaction monitoring mass spectrometry. The molecular weights of the identified differentially abundant proteins indicated an increased transport across the blood-brain barrier (BBB) at the peak of the disease, caused by an increase in BBB permeability. PMID:22320401

  19. Proteomic Analysis of Cerebrospinal Fluid in a Fulminant Case of Multiple Sclerosis

    PubMed Central

    Füvesi, Judit; Hanrieder, Jörg; Bencsik, Krisztina; Rajda, Cecilia; Kovács, S. Krisztián; Kaizer, László; Beniczky, Sándor; Vécsei, László; Bergquist, Jonas

    2012-01-01

    Multiple Sclerosis (MS) is a chronic disease, but in rare fulminant cases rapid progression may lead to death shortly after diagnosis. Currently there is no diagnostic test to predict disease course. The aim of this study was to identify potential biomarkers/proteins related to rapid progression. We present the case history of a 15-year-old male MS patient. Cerebrospinal fluid (CSF) was taken at diagnosis and at the time of rapid progression leading to the patient’s death. Using isobaric tag labeling and nanoflow liquid chromatography in conjunction with matrix assisted laser desorption/ionization time of flight tandem mass spectrometry we quantitatively analyzed the protein content of two CSF samples from the patient with fulminant MS as well as one relapsing-remitting (RR) MS patient and one control headache patient, whose CSF analysis was normal. Seventy-eight proteins were identified and seven proteins were found to be more abundant in both fulminant MS samples but not in the RR MS sample compared to the control. These proteins are involved in the immune response, blood coagulation, cell proliferation and cell adhesion. In conclusion, in this pilot study we were able to show differences in the CSF proteome of a rapidly progressing MS patient compared to a more typical clinical form of MS and a control subject. PMID:22837721

  20. Cytokines in the Cerebrospinal Fluids of Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

    PubMed Central

    Peterson, D.; Brenu, E. W.; Gottschalk, G.; Nguyen, T.; Marshall-Gradisnik, S.

    2015-01-01

    Objectives. Previous research has provided evidence for dysregulation in peripheral cytokines in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). To date only one study has examined cytokines in cerebrospinal fluid (CSF) samples of CFS/ME patients. The purpose of this pilot study was to examine the role of cytokines in CSF of CFS/ME patients. Methods. CSF was collected from 18 CFS/ME patients and 5 healthy controls. The CSF samples were examined for the expression of 27 cytokines (interleukin- (IL-) 1?, IL-1ra, IL-2, IL-4, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17, basic FGF, eotaxin, G-CSF, GM-CSF, IFN-?, IP-10, MCP-1 (MCAF), MIP-1?, MIP-1?, PDGF-BB, RANTES, TNF-?, and VEGF) using the Bio-Plex Human Cytokine 27-plex Assay. Results. Of the 27 cytokines examined, only IL-10 was significantly reduced in the CFS/ME patients in comparison to the controls. Conclusions. This preliminary investigation suggests that perturbations in inflammatory cytokines in the CSF of CFS/ME patients may contribute to the neurological discrepancies observed in CFS/ME. PMID:25834308

  1. Evidence for Fungal Infection in Cerebrospinal Fluid and Brain Tissue from Patients with Amyotrophic Lateral Sclerosis

    PubMed Central

    Alonso, Ruth; Pisa, Diana; Marina, Ana Isabel; Morato, Esperanza; Rábano, Alberto; Rodal, Izaskun; Carrasco, Luis

    2015-01-01

    Among neurogenerative diseases, amyotrophic lateral sclerosis (ALS) is a fatal illness characterized by a progressive motor neuron dysfunction in the motor cortex, brainstem and spinal cord. ALS is the most common form of motor neuron disease; yet, to date, the exact etiology of ALS remains unknown. In the present work, we have explored the possibility of fungal infection in cerebrospinal fluid (CSF) and in brain tissue from ALS patients. Fungal antigens, as well as DNA from several fungi, were detected in CSF from ALS patients. Additionally, examination of brain sections from the frontal cortex of ALS patients revealed the existence of immunopositive fungal antigens comprising punctate bodies in the cytoplasm of some neurons. Fungal DNA was also detected in brain tissue using PCR analysis, uncovering the presence of several fungal species. Finally, proteomic analyses of brain tissue demonstrated the occurrence of several fungal peptides. Collectively, our observations provide compelling evidence of fungal infection in the ALS patients analyzed, suggesting that this infection may play a part in the etiology of the disease or may constitute a risk factor for these patients.

  2. Immunocytochemical demonstration of feline infectious peritonitis virus within cerebrospinal fluid macrophages.

    PubMed

    Ives, Edward J; Vanhaesebrouck, An E; Cian, Francesco

    2013-12-01

    A 4-month-old female entire domestic shorthair cat presented with an acute onset of blindness, tetraparesis and subsequent generalised seizure activity. Haematology and serum biochemistry demonstrated a moderate, poorly regenerative anaemia, hypoalbuminaemia and hyperglobulinaemia with a low albumin:globulin ratio. Serology for feline coronavirus antibody was positive with an elevated alpha-1 acid glycoprotein. Analysis of cisternal cerebrospinal fluid (CSF) demonstrated markedly elevated protein and a mixed, predominately neutrophilic pleocytosis. Immunocytochemistry for feline coronavirus was performed on the CSF, with positive staining observed inside macrophages. The cat was subsequently euthanased, and both histopathology and immunohistochemistry were consistent with a diagnosis of feline infectious peritonitis. This is the first reported use of immunocytochemistry for detection of feline coronavirus within CSF macrophages. If this test proves highly specific, as for identification of feline coronavirus within tissue or effusion macrophages, it would be strongly supportive of an ante-mortem diagnosis of feline infectious peritonitis in cats with central nervous system involvement without the need for biopsy. PMID:23744728

  3. Endotoxins in the blood and cerebrospinal fluid of patients with African sleeping sickness.

    PubMed

    Pentreath, V W; Alafiatayo, R A; Crawley, B; Doua, F; Oppenheim, B A

    1996-01-01

    Endotoxin levels were measured in the blood and cerebrospinal fluid (CSF) of control individuals and 2 groups of patients with African sleeping sickness. Endotoxin levels were markedly elevated in the blood (infected groups mean endotoxin values 40.2 pg/ml and 53.8 pg/ml, compared to control 11.6 pg/ml, P < 0.0001 for both increases) and CSF (infected groups mean endotoxin values 45.8 pg/ml and 50.1 pg/ml compared to control 6.3 pg/ml, P < 0.0001 for both increases) of the patients. The levels were reduced 6 weeks following different drug treatments in the 2 groups (blood levels to mean 33.8 pg/ml and 28.5 pg/ml; CSF levels to 37.4 pg/ml and 27.0 pg/ml). The blood endotoxin values correlated with the CSF values before treatment (r = 0.74 and 0.57 for the 2 groups; P < 0.0001 for both) and after treatment (r = 0.57 and 0.56 for the 2 groups; P < 0.0001 for both). It is concluded that raised endotoxin equilibrates in the blood and CSF compartments, and may contribute significantly to the pathology of sleeping sickness. PMID:8587803

  4. Role of Cerebrospinal Fluid Biomarkers in Clinical Trials for Alzheimer's Disease Modifying Therapies

    PubMed Central

    Ryoo, Na-Young; Shin, Dong Wun; Trojanowski, John Q

    2014-01-01

    Until now, a disease-modifying therapy (DMT) that has an ability to slow or arrest Alzheimer's disease (AD) progression has not been developed, and all clinical trials involving AD patients enrolled by clinical assessment alone also have not been successful. Given the growing consensus that the DMT is likely to require treatment initiation well before full-blown dementia emerges, the early detection of AD will provide opportunities to successfully identify new drugs that slow the course of AD pathology. Recent advances in early detection of AD and prediction of progression of the disease using various biomarkers, including cerebrospinal fluid (CSF) A?1-42, total tau and p-tau181 levels, and imagining biomarkers, are now being actively integrated into the designs of AD clinical trials. In terms of therapeutic mechanisms, monitoring these markers may be helpful for go/no-go decision making as well as surrogate markers for disease severity or progression. Furthermore, CSF biomarkers can be used as a tool to enrich patients for clinical trials with prospect of increasing statistical power and reducing costs in drug development. However, the standardization of technical aspects of analysis of these biomarkers is an essential prerequisite to the clinical uses. To accomplish this, global efforts are underway to standardize CSF biomarker measurements and a quality control program supported by the Alzheimer's Association. The current review summarizes therapeutic targets of developing drugs in AD pathophysiology, and provides the most recent advances in the PMID:25598657

  5. Examination of deposits in cerebrospinal fluid shunt valves using scanning electron microscopy.

    PubMed

    Charalambides, Constantinos; Sgouros, Spyros

    2012-01-01

    Obstruction remains the most common complication of cerebrospinal fluid shunts. The valve constitutes an important site of potential malfunction. The aim of this pilot study was to investigate the extent and composition of debris depositions along the structural components of the shunt valve.We examined three explanted Medos programmable valves. The valves were stored and examined wet. They were cut open and disassembled. All specimens were studied under a scanning electron microscope (SEM; Quanta 200; FEI, Hillsboro, OR, USA) operating at different levels of accelerating voltage and 110 ?A beam current. Valve areas analyzed included the ruby ball and collar, the flat spring with its pillar, and the staircase cam. The elemental composition, in areas with abnormal deposits, was subsequently determined by energy-dispersive X-ray microanalysis (EDS) using a Si (Li) detector (Sapphire; EDAX, Mahwah, NJ, USA) with a super ultrathin Be window.All explanted valves had varying degrees of deposits in all surveyed areas. The extent of the deposits was not related to the time since implantation. The effect of these deposits on proper functioning of the valve as well as their pathogenesis is difficult to establish. PMID:22116429

  6. Partial characterization of a novel endogenous opioid in human cerebrospinal fluid

    SciTech Connect

    Miller, B.E.; Lipman, J.J.; Byrne, W.L.

    1987-12-07

    Human cerebrospinal fluid (CSF) contains many uncharacterized endogenous opioids, in addition to the known enkephalins, endorphins, and dynorphins. These opioids may be separated by gel filtration chromatography and identified by radioreceptor assay for opioid activity. One region of the chromatographic elution profile, designated Peak B has previously been shown to be related to the pain status of chronic pain patients. The authors now report that human Peak B isolated from the CSF of pain-free elective surgery patients is present at a typical concentration equivalent in activity to 1.4 pmol of morphine sulfate per ml of CSF measured by radioreceptor assay. At a dose of 0.06 and 0.12 pmol morphine sulfate equivalents of CSF (MSE), injected into the cerebroventricular system of the mouse, Peak B produced an antinociceptive effect, the intensity and duration of which was dose-dependent and which was antagonized by naloxone. The mouse vas deferens (MVD) preparation was inhibited by Peak B in a manner that was sensitive to antagonism by naloxone only at low (< 1.0 ..mu..M) but not at higher (>6.0 ..mu..M) concentrations of the antagonist. Peak B activity in the MVD assay was unaffected by treatment with trypsin or ..cap alpha..-chymotrypsin. 32 references, 4 figures, 1 table.

  7. Plasma and cerebrospinal fluid progesterone concentrations in pregnant and nonpregnant women.

    PubMed

    Datta, S; Hurley, R J; Naulty, J S; Stern, P; Lambert, D H; Concepcion, M; Tulchinsky, D; Weiss, J B; Ostheimer, G W

    1986-09-01

    Pregnancy is associated with a wider dermatomal spread of local anesthetics after epidural and spinal anesthesia. This phenomenon also exists in the immediate postpartum period. The mechanism of this observation is unresolved. However, an increase in progesterone concentration in pregnancy has been implicated as one of the factors. Although plasma progesterone concentrations in humans have been well-documented, the cerebrospinal fluid (CSF) progesterone levels, which may also be important in this regard, have not been determined. Therefore, this study was undertaken to measure plasma and CSF progesterone in the nonpregnant, term parturient and in the immediate postpartum patient and also to determine the relationship between the CSF progesterone concentration and the intrathecal spread of lidocaine used for spinal anesthesia. The plasma progesterone concentrations in 12 nonpregnant, 21 term and eight postpartum patients were 2.3 +/- 61 (SEM) ng/ml, 122 +/- 8 ng/ml and 16 +/- 2.2 ng/ml, respectively. The CSF progesterone concentrations in term parturients (3 +/- 0.28 (SEM) ng/ml) and postpartum patients (1.03 +/- 0.16 ng/ml) were eight and three times greater than that of nonpregnant women (0.39 +/- 0.01 ng/ml). Significantly less lidocaine was needed (P less than 0.05) for comparable segmental levels of spinal anesthesia in term and postpartum patients than in nonpregnant individuals. These data suggest that high CSF, plasma progesterone concentrations, or both may augment the anesthetic spread of lidocaine. PMID:3740493

  8. Approach to Cerebrospinal Fluid (CSF) Biomarker Discovery and Evaluation in HIV Infection

    SciTech Connect

    Price, Richard W.; Peterson, Julia; Fuchs, Dietmar; Angel, Thomas E.; Zetterberg, Henrik; Hagberg, Lars; Spudich, Serena S.; Smith, Richard D.; Jacobs, Jon M.; Brown, Joseph N.; Gisslen, Magnus

    2013-12-13

    Central nervous system (CNS) infection is a nearly universal facet of systemic HIV infection that varies in character and neurological consequences. While clinical staging and neuropsychological test performance have been helpful in evaluating patients, cerebrospinal fluid (CSF) biomarkers present a valuable and objective approach to more accurate diagnosis, assessment of treatment effects and understanding of evolving pathobiology. We review some lessons from our recent experience with CSF biomarker studies. We have used two approaches to biomarker analysis: targeted, hypothesis-driven and non-targeted exploratory discovery methods. We illustrate the first with data from a cross-sectional study of defined subject groups across the spectrum of systemic and CNS disease progression and the second with a longitudinal study of the CSF proteome in subjects initiating antiretroviral treatment. Both approaches can be useful and, indeed, complementary. The first is helpful in assessing known or hypothesized biomarkers while the second can identify novel biomarkers and point to broad interactions in pathogenesis. Common to both is the need for well-defined samples and subjects that span a spectrum of biological activity and biomarker concentrations. Previouslydefined guide biomarkers of CNS infection, inflammation and neural injury are useful in categorizing samples for analysis and providing critical biological context for biomarker discovery studies. CSF biomarkers represent an underutilized but valuable approach to understanding the interactions of HIV and the CNS and to more objective diagnosis and assessment of disease activity. Both hypothesis-based and discovery methods can be useful in advancing the definition and use of these biomarkers.

  9. Analysis of brain nuclei accessible to ghrelin present in the cerebrospinal fluid.

    PubMed

    Cabral, A; Fernandez, G; Perello, M

    2013-12-01

    Ghrelin is a stomach-derived peptide hormone that acts in the brain to regulate many important physiological functions. Ghrelin receptor, named the growth hormone secretagogue receptor (GHSR), is present in many brain areas with or without obvious direct access to ghrelin circulating in the bloodstream. Ghrelin is also present in the cerebrospinal fluid (CSF) but the brain targets of CSF ghrelin are unclear. Here, we studied which brain areas are accessible to ghrelin present in the CSF. For this purpose, we centrally injected mice with fluorescein-labeled ghrelin (F-ghrelin) peptide tracer and then systematically mapped the distribution of F-ghrelin signal through the brain. Our results indicated that centrally injected F-ghrelin labels neurons in most of the brain areas where GHSR is present. Also, we detected F-ghrelin uptake in the ependymal cells of both wild-type and GHSR-null mice. We conclude that CSF ghrelin is able to reach most of brain areas expressing GHSR. Also, we propose that the accessibility of CSF ghrelin to the brain parenchyma occurs through the ependymal cells in a GHSR-independent manner. PMID:24042041

  10. Clonally expanded plasma cells in the cerebrospinal fluid of MS patients produce myelin-specific antibodies.

    PubMed

    von Büdingen, Hans-Christian; Harrer, Melanie D; Kuenzle, Sandra; Meier, Mirjam; Goebels, Norbert

    2008-07-01

    Clonally expanded plasma cells (cePC) and their presumed products, oligoclonal immunoglobulin G bands (OCB), are characteristic findings in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS). While cePC and OCB strongly suggest an involvement of B cell-dependent immune mechanisms in the pathogenesis of MS, their actual pathological relevance and target antigens remain unknown. To further understand the potential role played by cePC, we generated a panel of monoclonal antibodies (MS-mAb) from CSF-derived cePC from four patients with early or definite MS. Single-cell RT-PCR of correctly paired heavy and light chain immunoglobulin genes from individual cePC ensured the subsequent resurrection of their original antigen specificity. Immunofluorescence stainings of MS lesion tissue with MS-mAb revealed myelin reactivity in the cePC repertoire of all four patients and intracellular filament reactivity in one patient. While myelin staining by MS-mAb was only rarely detectable in non-MS CNS white matter tissue, it was greatly enhanced at the edge of demyelinating lesions in MS brain tissue. Our findings provide conclusive evidence for the presence of an antigen-driven B cell response in the CSF of MS patients directed against epitopes present in areas of myelin degradation. PMID:18521957

  11. Mechanism for measurement of flow rate of cerebrospinal fluid in hydrocephalus shunts.

    PubMed

    Rajasekaran, Sathish; Kovar, Spencer; Qu, Peng; Inwald, David; Williams, Evan; Qu, Hongwei; Zakalik, Karol

    2014-01-01

    The measurement of the flow rate of cerebrospinal fluid (CSF) or existence of CSF flow inside the shunt tube after shunt implant have been reported as tedious process for both patients and doctors; this paper outlines a potential in vitro flow rate measurement method for CSF in the hydrocephalus shunt. The use of implantable titanium elements in the shunt has been proposed to allow for an accurate temperature measurement along the shunt for prediction of CSF flow rate. The CSF flow velocity can be deduced by decoupling the thermal transfer in the measured differential time at a pair of measurement spots of the titanium elements. Finite element analyses on the fluidic and thermal behaviors of the shunt system have been conducted. Preliminary bench-top measurements on a simulated system have been carried out. The measured flow rates, ranging from 0.5 mm/sec to 1.0 mm/sec, which is clinically practical, demonstrate good agreements with the simulation results. PMID:25570411

  12. Effects of Blood Contamination and the Rostro-Caudal Gradient on the Human Cerebrospinal Fluid Proteome

    PubMed Central

    Aasebø, Elise; Opsahl, Jill Anette; Bjørlykke, Yngvild; Myhr, Kjell-Morten; Kroksveen, Ann Cathrine; Berven, Frode S.

    2014-01-01

    Over the last years there has been an increased focus on the importance of knowing the effect of pre-analytical influence on the proteomes under study, particularly in the field of biomarker discovery. We present three proteomics studies examining the effect of blood contamination and the rostro-caudal gradient (RCG) on the cerebrospinal fluid (CSF) proteome, in addition to plasma/CSF protein ratios. The studies showed that the central nervous system (CNS) derived proteins appeared to be unaffected by the RCG, while the plasma-derived proteins showed an increase in concentration towards the lumbar area. This implies that the concentration of the plasma-derived proteins in CSF will vary depending on the volume of CSF that is collected. In the CSF samples spiked with blood, 262 of 814 quantified proteins showed an abundance increase of more than 1.5 fold, while 403 proteins had a fold change of less than 1.2 and appeared to be unaffected by blood contamination. Proteins with a high plasma/CSF ratio appeared to give the largest effect on the CSF proteome upon blood contamination. The results give important background information on how factors like blood contamination, RCG and blood-CNS-barrier influences the CSF proteome. This information is particularly important in the field of biomarker discovery, but also for routine clinical measurements. The data from the blood contamination and RCG discovery studies have been deposited to the ProteomeXchange with identifier PXD000401. PMID:24599184

  13. Cerebrospinal fluid–based kinetic biomarkers of axonal transport in monitoring neurodegeneration

    PubMed Central

    Fanara, Patrizia; Wong, Po-Yin A.; Husted, Kristofor H.; Liu, Shanshan; Liu, Victoria M.; Kohlstaedt, Lori A.; Riiff, Timothy; Protasio, Joan C.; Boban, Drina; Killion, Salena; Killian, Maudi; Epling, Lorrie; Sinclair, Elisabeth; Peterson, Julia; Price, Richard W.; Cabin, Deborah E.; Nussbaum, Robert L.; Brühmann, Jörg; Brandt, Roland; Christine, Chadwick W.; Aminoff, Michael J.; Hellerstein, Marc K.

    2012-01-01

    Progress in neurodegenerative disease research is hampered by the lack of biomarkers of neuronal dysfunction. We here identified a class of cerebrospinal fluid–based (CSF-based) kinetic biomarkers that reflect altered neuronal transport of protein cargo, a common feature of neurodegeneration. After a pulse administration of heavy water (2H2O), distinct, newly synthesized 2H-labeled neuronal proteins were transported to nerve terminals and secreted, and then appeared in CSF. In 3 mouse models of neurodegeneration, distinct 2H-cargo proteins displayed delayed appearance and disappearance kinetics in the CSF, suggestive of aberrant transport kinetics. Microtubule-modulating pharmacotherapy normalized CSF-based kinetics of affected 2H-cargo proteins and ameliorated neurodegenerative symptoms in mice. After 2H2O labeling, similar neuronal transport deficits were observed in CSF of patients with Parkinson’s disease (PD) compared with non-PD control subjects, which indicates that these biomarkers are translatable and relevant to human disease. Measurement of transport kinetics may provide a sensitive method to monitor progression of neurodegeneration and treatment effects. PMID:22922254

  14. Ultrasound-guided atlanto-occipital puncture for cerebrospinal fluid analysis on the standing horse.

    PubMed

    Depecker, M; Bizon-Mercier, C; Couroucé-Malblanc, A

    2014-01-11

    The atlanto-occipital site (AO) is convenient for retrieving an adequate volume and quality of cerebrospinal fluid (CSF) in the diagnosis of neurological disease in horses. However, general anaesthesia is not always possible for horses displaying severe neurological signs, or for economical reasons. The objectives of the present work were to determine the feasibility and safety of ultrasound-guided CSF puncture at the AO site on the standing horse. Seven horses (six healthy and one mildly ataxic) were sedated with acepromazine (0.02 mg/kg bodyweight intravenously or 0.04 mg/kg bodyweight intramuscularly) and detomidine (0.01 mg/kg bodyweight intravenously), and placed in stocks or in a recovery stall with the head kept on a headstand. Puncture was performed by ultrasonographic guidance with a parasagittal technique, as previously described, using a 20 g, 3.5 inch spinal needle. In all horses, no adverse reaction was observed when crossing the dura mater and 20 ml of CSF was rapidly retrieved without any blood contamination. Ultrasound-guided CSF puncture can be performed easily at the AO site on a healthy standing horse. Regarding the potential risk of this procedure, safety measures and close observation are essential. Further studies on a larger amount of ataxic horses are also required before considering this technique as an alternative option for CSF puncture. PMID:24225443

  15. Cerebrospinal fluid Th1/Th2 cytokine profiles in children with enterovirus 71-associated meningoencephalitis.

    PubMed

    Li, Huajun; Li, Shuxian; Zheng, Jianfeng; Cai, Chunyan; Ye, Bin; Yang, Jun; Chen, Zhimin

    2015-03-01

    Enterovirus 71 (EV71) infection can cause severe neurological complications including meningoencephalitis (ME) in some patients with hand, foot and mouth disease (HFMD). However, to date no studies have reported changes in cytokine concentrations and their correlations with clinical variables in patients with ME following EV71 infection. In this study, responses of Th1/Th2 cytokine, including IL-2, IL-4, IL-6, IL-10, TNF-? and IFN-?, in cerebrospinal fluid (CSF) from patients with EV71-related HFMD with ME and patients with febrile convulsions (FC) were analyzed using cytometric bead array technology. It was found that CSF IL-6 and IFN-? concentrations were significantly higher in patients with EV71-related ME than in those with FC. Additionally, both CSF IL-6 and IFN-? concentrations were correlated with CSF cytology, fever duration and duration of hospital stay. More interestingly, a positive correlation between CSF IL-6 and IFN-? concentrations was observed. Finally, receiver operating characteristic analysis revealed that when a cutoff value of 9.40?pg/mL was set for IL-6, the sensitivity and specificity were 84.5% and 85.5%, respectively, for discriminating EV71-related ME from FC. In conclusion, IL-6 and IFN-? may be associated with EV71-induced neuropathology. PMID:25611005

  16. Homocysteine and methylmalonic acid concentrations in cerebrospinal fluid: relation with age and Alzheimer's disease

    PubMed Central

    Serot, J; Barbe, F; Arning, E; Bottiglieri, T; Franck, P; Montagne, P; Nicolas, J

    2005-01-01

    Objectives: To compare cerebrospinal fluid (CSF) total homocysteine and MMA in elderly subjects, patients with Alzheimer's disease, and younger healthy controls. Subjects: CSF samples were obtained from 33 patients under 20 years of age; 28 patients aged 21 to 60 years; 22 normal elderly subjects aged over 60; and 38 Alzheimer patients aged over 60. Results: CSF total homocysteine increased with age (mean (SD): 57 (35) nmol/l in the youngest group v 123 (89) nmol/l in the elderly group (p<0.001)) There was no difference between the elderly group and Alzheimer patients (115 (62) nmol/l). CSF MMA did not differ in the elderly group and the Alzheimer group (38 (13) v 35 (14) ng/ml). In the youngest group, it was significantly higher (60 (15) ng/ml). Conclusions: CSF total homocysteine is not increased in Alzheimer's disease compared with age matched controls. CSF total homocysteine was correlated with age. The decrease in CSF MMA levels with age eliminates a lack of vitamin B-12 at neuronal level. PMID:16227558

  17. Meningeal Melanomatosis: A Challenge for Timely Diagnosis

    PubMed Central

    Di Stefano, Anna Luisa; Bini, Paola; Imarisio, Ilaria; Magrassi, Lorenzo; Morbini, Patrizia; Farina, Lisa Maria; Bastianello, Stefano; Ceroni, Mauro; Marchioni, Enrico

    2015-01-01

    Neoplastic meningitis is a central nervous system complication that occurs in 3–5% of patients with cancer. Although most commonly seen in patients with disseminated disease, in a small percentage of patients, it may be the initial manifestation of cancer or even primitive in origin. In the absence of cancer history, the diagnosis of neoplastic meningitis may be challenging even for expert neurologists. Prognosis is poor, with a median overall survival of weeks from diagnosis. In the retrospective study herein, we described three cases of meningeal melanomatosis in patients without previous cancer history. The patients were diagnosed with significant delay (17 to 47 weeks from symptom onset) mainly due to the deferral in performing the appropriate testing. Even when the diagnosis was suspected, investigations by MRI, cerebrospinal fluid, or both proved at times unhelpful for confirmation. Prognosis was dismal, with a median survival of 4 weeks after diagnosis. Our observations are a cue to analyze the main pitfalls in the diagnosis of neoplastic meningitis in patients without cancer history and emphasize key elements that may facilitate early diagnosis. PMID:25648721

  18. Pathogenesis and Pathophysiology of Pneumococcal Meningitis

    PubMed Central

    Mook-Kanamori, Barry B.; Geldhoff, Madelijn; van der Poll, Tom; van de Beek, Diederik

    2011-01-01

    Summary: Pneumococcal meningitis continues to be associated with high rates of mortality and long-term neurological sequelae. The most common route of infection starts by nasopharyngeal colonization by Streptococcus pneumoniae, which must avoid mucosal entrapment and evade the host immune system after local activation. During invasive disease, pneumococcal epithelial adhesion is followed by bloodstream invasion and activation of the complement and coagulation systems. The release of inflammatory mediators facilitates pneumococcal crossing of the blood-brain barrier into the brain, where the bacteria multiply freely and trigger activation of circulating antigen-presenting cells and resident microglial cells. The resulting massive inflammation leads to further neutrophil recruitment and inflammation, resulting in the well-known features of bacterial meningitis, including cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema, hydrocephalus, and cerebrovascular complications. Experimental animal models continue to further our understanding of the pathophysiology of pneumococcal meningitis and provide the platform for the development of new adjuvant treatments and antimicrobial therapy. This review discusses the most recent views on the pathophysiology of pneumococcal meningitis, as well as potential targets for (adjunctive) therapy. PMID:21734248

  19. Predictive Value of Decoy Receptor 3 in Postoperative Nosocomial Bacterial Meningitis

    PubMed Central

    Liu, Yong-Juan; Shao, Li-Hua; Wang, Qian; Zhang, Jian; Ma, Rui-Ping; Liu, Hai-Hong; Dong, Xiao-Meng; Ma, Li-Xian

    2014-01-01

    Nosocomial bacterial meningitis requires timely treatment, but what is difficult is the prompt and accurate diagnosis of this disease. The aim of this study was to assess the potential role of decoy receptor 3 (DcR3) levels in the differentiation of bacterial meningitis from non-bacterial meningitis. A total of 123 patients were recruited in this study, among them 80 patients being with bacterial meningitis and 43 patients with non-bacterial meningitis. Bacterial meningitis was confirmed by bacterial culture of cerebrospinal fluid (CSF) culture and enzyme-linked immunosorbent assay (ELISA) was used to detect the level of DcR3 in CSF. CSF levels of DcR3 were statistically significant between patients with bacterial meningitis and those with non-bacterial meningitis (p < 0.001). A total of 48.75% of patients with bacterial meningitis received antibiotic >24 h before CSF sampling, which was much higher than that of non-bacterial meningitis. CSF leucocyte count yielded the highest diagnostic value, with an area under the receiver operating characteristic curve (ROC) of 0.928, followed by DcR3. At a critical value of 0.201 ng/mL for DcR3, the sensitivity and specificity were 78.75% and 81.40% respectively. DcR3 in CSF may be a valuable predictor for differentiating patients with bacterial meningitis from those with non-bacterial meningitis. Further studies are needed for the validation of this study. PMID:25372942

  20. Insights into pediatric diffuse intrinsic pontine glioma through proteomic analysis of cerebrospinal fluid

    PubMed Central

    M. Saratsis, Amanda; Yadavilli, Sridevi; Magge, Suresh; Rood, Brian R.; Perez, Jennifer; Hill, D. Ashley; Hwang, Eugene; Kilburn, Lindsay; Packer, Roger J.; Nazarian, Javad

    2012-01-01

    Diffuse intrinsic pontine glioma (DIPG) is a leading cause of brain tumor–related death in children. DIPG is not surgically resectable, resulting in a paucity of tissue available for molecular studies. As such, tumor biology is poorly understood, and, currently, there are no effective treatments. In the absence of frozen tumor specimens, body fluids—such as cerebrospinal fluid (CSF), serum, and urine—can serve as more readily accessible vehicles for detecting tumor-secreted proteins. We analyzed a total of 76 specimens, including CSF, serum, urine, and normal and tumor brainstem tissue. Protein profiling of CSF from patients with DIPG was generated by mass spectrometry using an LTQ-Orbitrap-XL and database search using the Sequest algorithm. Quantitative and statistical analyses were performed with ProteoIQ and Partek Genomics Suite. A total of 528 unique proteins were identified, 71% of which are known secreted proteins. CSF proteomic analysis revealed selective upregulation of Cyclophillin A (CypA) and dimethylarginase 1 (DDAH1) in DIPG (n = 10), compared with controls (n = 4). Protein expression was further validated with Western blot analysis and immunohistochemical assays using CSF, brain tissue, serum, and urine from DIPG and control specimens. Immunohistochemical staining showed selective upregulation of secreted but not cytosolic CypA and DDAH1 in patients with DIPG. In this study, we present the first comprehensive protein profile of CSF specimens from patients with DIPG to demonstrate selective expression of tumor proteins potentially involved in brainstem gliomagenesis. Detection of secreted CypA and DDAH1 in serum and urine has potential clinical application, with implications for assessing treatment response and detecting tumor recurrence in patients with DIPG. PMID:22492959

  1. MicroRNAs in cerebrospinal fluid identify glioblastoma and metastatic brain cancers and reflect disease activity

    PubMed Central

    Teplyuk, Nadiya M.; Mollenhauer, Brit; Gabriely, Galina; Giese, Alf; Kim, Ella; Smolsky, Michael; Kim, Ryan Y.; Saria, Marlon G.; Pastorino, Sandra; Kesari, Santosh; Krichevsky, Anna M.

    2012-01-01

    An accurate, nonsurgical diagnostic test for brain tumors is currently unavailable, and the methods of monitoring disease progression are not fully reliable. MicroRNA profiling of biological fluids has recently emerged as a diagnostic tool for several pathologic conditions. Here we tested whether microRNA profiling of cerebrospinal fluid (CSF) enables detection of glioblastoma, discrimination between glioblastoma and metastatic brain tumors, and reflects disease activity. We determined CSF levels of several cancer-associated microRNAs for 118 patients diagnosed with different types of brain cancers and nonneoplastic neuropathologies by quantitative reverse transcription PCR analysis. The levels of miR-10b and miR-21 are found significantly increased in the CSF of patients with glioblastoma and brain metastasis of breast and lung cancer, compared with tumors in remission and a variety of nonneoplastic conditions. Members of the miR-200 family are highly elevated in the CSF of patients with brain metastases but not with any other pathologic conditions, allowing discrimination between glioblastoma and metastatic brain tumors. Quantification of as few as 7 microRNAs in CSF enables differential recognition of glioblastoma and metastatic brain cancer using computational machine learning tools (Support Vector Machine) with high accuracy (91%–99%) on a test set of samples. Furthermore, we show that disease activity and treatment response can be monitored by longitudinal microRNA profiles in the CSF of glioblastoma and non–small cell lung carcinoma patients. This study demonstrates that microRNA-based detection of brain malignancies can be reliably performed and that microRNAs in CSF can serve as biomarkers of treatment response in brain cancers. PMID:22492962

  2. Prion-Seeding Activity in Cerebrospinal Fluid of Deer with Chronic Wasting Disease

    PubMed Central

    Haley, Nicholas J.; Van de Motter, Alexandra; Carver, Scott; Henderson, Davin; Davenport, Kristen; Seelig, Davis M.; Mathiason, Candace; Hoover, Edward

    2013-01-01

    Transmissible spongiform encephalopathies (TSEs), or prion diseases, are a uniformly fatal family of neurodegenerative diseases in mammals that includes chronic wasting disease (CWD) of cervids. The early and ante-mortem identification of TSE-infected individuals using conventional western blotting or immunohistochemistry (IHC) has proven difficult, as the levels of infectious prions in readily obtainable samples, including blood and bodily fluids, are typically beyond the limits of detection. The development of amplification-based seeding assays has been instrumental in the detection of low levels of infectious prions in clinical samples. In the present study, we evaluated the cerebrospinal fluid (CSF) of CWD-exposed (n=44) and naïve (n=4) deer (n=48 total) for CWD prions (PrPd) using two amplification assays: serial protein misfolding cyclic amplification with polytetrafluoroethylene beads (sPMCAb) and real-time quaking induced conversion (RT-QuIC) employing a truncated Syrian hamster recombinant protein substrate. Samples were evaluated blindly in parallel with appropriate positive and negative controls. Results from amplification assays were compared to one another and to obex immunohistochemistry, and were correlated to available clinical histories including CWD inoculum source (e.g. saliva, blood), genotype, survival period, and duration of clinical signs. We found that both sPMCAb and RT-QuIC were capable of amplifying CWD prions from cervid CSF, and results correlated well with one another. Prion seeding activity in either assay was observed in approximately 50% of deer with PrPd detected by IHC in the obex region of the brain. Important predictors of amplification included duration of clinical signs and time of first tonsil biopsy positive results, and ultimately the levels of PrPd identified in the obex by IHC. Based on our findings, we expect that both sPMCAb and RT-QuIC may prove to be useful detection assays for the detection of prions in CSF. PMID:24282599

  3. A computational model of cerebrospinal fluid production and reabsorption driven by Starling forces

    PubMed Central

    Buishas, Joel; Gould, Ian G.; Linninger, Andreas A.

    2014-01-01

    Experimental evidence has cast doubt on the classical model of river-like cerebrospinal fluid (CSF) flow from the choroid plexus to the arachnoid granulations. We propose a novel model of water transport through the parenchyma from the microcirculation as driven by Starling forces. This model investigates the effect of osmotic pressure on water transport between the cerebral vasculature, the extracellular space (ECS), the perivascular space (PVS), and the CSF. A rigorous literature search was conducted focusing on experiments which alter the osmolarity of blood or ventricles and measure the rate of CSF production. Investigations into the effect of osmotic pressure on the volume of ventricles and the flux of ions in the blood, choroid plexus epithelium, and CSF are reviewed. Increasing the osmolarity of the serum via a bolus injection completely inhibits nascent fluid flow production in the ventricles. A continuous injection of a hyperosmolar solution into the ventricles can increase the volume of the ventricle by up to 125%. CSF production is altered by 0.231 µL per mOsm in the ventricle and by 0.835 µL per mOsm in the serum. Water flux from the ECS to the CSF is identified as a key feature of intracranial dynamics. A complete mathematical model with all equations and scenarios is fully described, as well as a guide to constructing a computational model of intracranial water balance dynamics. The model proposed in this article predicts the effects the osmolarity of ECS, blood, and CSF on water flux in the brain, establishing a link between osmotic imbalances and pathological conditions such as hydrocephalus and edema. PMID:25358881

  4. Clinical and Laboratory Features of Streptococcus salivarius Meningitis: A Case Report and Literature Review

    PubMed Central

    Wilson, Megan; Martin, Ryan; Walk, Seth T.; Young, Carol; Grossman, Sylvia; McKean, Erin Lin; Aronoff, David M.

    2012-01-01

    Streptococcus salivarius is a normal member of the human oral microbiome that is an uncommon cause of invasive infections. Meningitis is a rare but increasingly reported infection caused by S. salivarius. Despite the growing number of reported cases, a comprehensive review of the literature on S. salivarius meningitis is lacking. We sought to gain a better understanding of the clinical presentation, evaluation, management, and outcome of S. salivarius meningitis by analyzing previously reported cases. In addition to a single case reported here, 64 previously published cases of meningitis were identified for this review. The collected data confirm that most patients presented with classical signs and symptoms of bacterial meningitis with a predominance of neutrophils in the cerebrospinal fluid (CSF) and hypoglycorrhachia. The majority of cases followed iatrogenic or traumatic CSF contamination. Most cases were diagnosed by CSF culture within one day of symptom onset. There was no clear evidence of predisposing co-morbid conditions in patients with meningitis, although in most case reports, limited information was given on the medical history of each patient. Outcomes were generally favorable with antibiotic management. Clinicians should suspect S. salivarius meningitis in patients presenting acutely after medical or surgical procedures involving the meninges. PMID:21817122

  5. Salmonella enterica serovar Virchow meningitis in a young man in Italy: a case report

    PubMed Central

    2014-01-01

    Introduction Salmonella enterica is a leading cause of foodborne infections worldwide and includes more than 2500 different serovars, causing primarily gastroenteritis. However, the infection may occur elsewhere and produce characteristic clinical syndromes. Meningitis is a rare complication that occurs in less than 1% of clinical salmonellosis. Case presentation We describe a case of Salmonella Virchow meningitis in a 36-year-old Caucasian man presenting with headache in the occipital region, associated fever, nausea and vomiting, dyspnea and ambulatory difficulty. The cerebrospinal fluid culture showed growth of Salmonella, later confirmed to be Salmonella enterica serovar Virchow. Conclusions Salmonella Virchow infection is rare and this report highlights the risk of meningitis as a presentation of salmonellosis. To the best of our knowledge this is the first Italian case of meningitis due to Salmonella Virchow in a young adult. The probable route of transmission remains unclear and a long carriage state after a previous episode of gastroenteritis should be considered. PMID:24884674

  6. Detection of single bacteria – causative agents of meningitis using raman microscopy

    NASA Astrophysics Data System (ADS)

    Baikova, T. V.; Minaeva, S. A.; Sundukov, A. V.; Svistunova, T. S.; Bagratashvili, V. N.; Alushin, M. V.; Gonchukov, S. A.

    2015-03-01

    Early diagnostics of meningitis is a very topical problem as it is a fulminant disease with a high level of mortality. The progress of this disease is, as a rule, accompanied by the appearance of bacteria in the cerebrospinal fluid (CSF) composition. The examination of the CSF is well known to be the only reliable approach to the identification of meningitis. However, the traditional biochemical analyses are time consuming and not always reliable, simple, and inexpensive, whereas the optical methods are poorly developed. This work is devoted to the study of Raman spectra of several bacterial cultures which are mainly present during meningitis. Raman microscopy is a prompt and noninvasive technique capable of providing reliable information about molecular-level alterations of biological objects at their minimal quantity and size. It was shown that there are characteristic lines in Raman spectra which can be the reliable markers for determination of bacterial form of meningitis at a level of a single bacterium.

  7. Visualisation of cerebrospinal fluid flow patterns in albino Xenopus larvae in vivo

    PubMed Central

    2012-01-01

    Background It has long been known that cerebrospinal fluid (CSF), its composition and flow, play an important part in normal brain development, and ependymal cell ciliary beating as a possible driver of CSF flow has previously been studied in mammalian fetuses in vitro. Lower vertebrate animals are potential models for analysis of CSF flow during development because they are oviparous. Albino Xenopus laevis larvae are nearly transparent and have a straight, translucent brain that facilitates the observation of fluid flow within the ventricles. The aim of these experiments was to study CSF flow and circulation in vivo in the developing brain of living embryos, larvae and tadpoles of Xenopus laevis using a microinjection technique. Methods The development of Xenopus larval brain ventricles and the patterns of CSF flow were visualised after injection of quantum dot nanocrystals and polystyrene beads (3.1 or 5.8 ?m in diameter) into the fourth cerebral ventricle at embryonic/larval stages 30-53. Results The fluorescent nanocrystals showed the normal development of the cerebral ventricles from embryonic/larval stages 38 to 53. The polystyrene beads injected into stage 47-49 larvae revealed three CSF flow patterns, left-handed, right-handed and non-biased, in movement of the beads into the third ventricle from the cerebral aqueduct (aqueduct of Sylvius). In the lateral ventricles, anterior to the third ventricle, CSF flow moved anteriorly along the outer wall of the ventricle to the inner wall and then posteriorly, creating a semicircle. In the cerebral aqueduct, connecting the third and fourth cerebral ventricles, CSF flow moved rostrally in the dorsal region and caudally in the ventral region. Also in the fourth ventricle, clear dorso-ventral differences in fluid flow pattern were observed. Conclusions This is the first visualisation of the orchestrated CSF flow pattern in developing vertebrates using a live animal imaging approach. CSF flow in Xenopus albino larvae showed a largely consistent pattern, with the exception of individual differences in left-right asymmetrical flow in the third ventricle. PMID:22534239

  8. Polymerase chain reaction analysis and oligoclonal antibody in the cerebrospinal fluid from 34 patients with varicella?zoster virus infection of the nervous system

    PubMed Central

    Gregoire, S M; van Pesch, V; Goffette, S; Peeters, A; Sindic, C J M

    2006-01-01

    Objective To study cerebrospinal fluid (CSF) and serum samples from 34 consecutive patients suspected of having varicella?zoster virus (VZV) infection of the central nervous system (CNS). Population and methods The patients were divided into three groups. The first group consisted of 27 patients with a rash in one to three dermatomes and clinical suspicion of meningitis and radiculitis; among them, three subgroups were distinguished according to the affected dermatome: ophthalmicus (n?=?9), oticus (n?=?11) and cervico?thoraco?lumbar zoster (n?=?7). Four cases of zoster sine herpete (ZSH) were included in the second group: these patients presented with either radiculitis (n?=?2) or meningoencephalitis (n?=?2), without cutaneous eruption. The third group consisted of three patients with a generalised rash and encephalitis. A polymerase chain reaction (PCR) for VZV DNA and antigen?driven immunoblots for oligoclonal anti?VZV antibodies were carried out on all CSF samples. Results PCR of the CSF was positive in 44% of the patients from the first group, mainly within the first 7?days after eruption. In addition, intrathecal synthesis of anti?VZV antibodies was detected in 37% of patients, always after an interval of 7?days (p<0.0001). Among the four patients with ZSH, a positive VZV PCR was detected in three patients and CSF?specific oligoclonal anti?VZV antibodies in two. PCR was also positive in the CSF of two of the three patients with generalised rash and encephalitis; local production of anti?VZV antibodies was seen in a second CSF sample in one patient, and was also present in the third patient. Conclusion Amplification of VZV DNA by PCR in the CSF and antigen?driven immunoblots have important diagnostic value in suspected VZV infection, although their presence depends on the timing of the CSF sampling. VZV is thought to be a causative agent in unexplained cases of meningitis associated with radiculitis or focal CNS symptoms, even in the absence of skin manifestations. In such patients, rapid diagnosis by this combined approach permits early antiviral treatment. PMID:16844949

  9. Diabetic Retinopathy and Estimated Cerebrospinal Fluid Pressure. The Beijing Eye Study 2011

    PubMed Central

    Wang, Ya Xing; You, Qi Sheng; Yang, Diya; Xie, Xiao Bin; Xu, Liang

    2014-01-01

    Purpose The cerebrospinal fluid pressure (CSFP) is a major determinant of central retinal vein pressure and thus of retinal capillary pressure. We tested the hypothesis whether prevalence and severity of diabetic retinopathy are associated with CSFP. Methods The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years. A detailed ophthalmic examination was performed including fundus photography for the assessment of diabetic retinopathy according. Based on a previous study with lumbar cerebrospinal fluid pressure (CSFP) measurements, CSFP was calculated as CSFP[mmHg]?=?0.44xBody Mass Index[kg/m2]+0.16 Diastolic Blood Pressure[mmHg]–0.18xAge[Years]?1.91. Results In binary regression analysis, presence of diabetic retinopathy was significantly associated with higher levels of HbA1c (P<0.001; regression coefficient B:0.25; odds ratio (OR):1.28; 95% confidence interval (CI):1.15,1.43), higher blood concentration of glucose (P<0.001; B:0.40;OR:1.49;95%CI:1.36,1.63), longer known duration of diabetes mellitus (P<0.001; B:0.14;OR:1.15; 95%CI:1.11,1.19), higher systolic blood pressure (P<0.001; B:0.03;OR:1.03;95%CI:1.02,1.04), lower diastolic blood pressure (P<0.001; B:?0.06;OR:0.94;95%CI:0.91,0.97), and higher CSFP (P?=?0.002; B:0.13;OR:1.14;95%CI:1.05,1.24). Severity of diabetic retinopathy was significantly associated with higher HbA1c value (P<0.001; standardized coefficient beta: 0.19; correlation coefficient B: 0.07;95%CI:0.05,0.08), higher blood concentration of glucose (P<0.001; beta:0.18;B:0.04;95%CI:0.04,0.05), longer known duration of diabetes mellitus (P<0.001; beta:0.20;B:0.03;95%CI:0.02,0.03), lower level of education (P?=?0.001; beta:?0.05;B:?0.02;95%CI:?0.03,?0.01), lower diastolic blood pressure (P?=?0.002; beta:?0.08;B:?0.001;95%CI:?0.004,?0.001), higher systolic blood pressure (P?=?0.006; beta:0.06;B:0.001;95%CI:0.000,0.001), and higher CSFP (P?=?0.006; beta:0.06;B:0.006;95%CI:0.002,0.010). Conclusions Higher prevalence and severity of diabetic retinopathy were associated with higher estimated CSFP after adjusting for systemic parameters. Higher CSFP through a higher retinal vein pressure may lead to more marked retinal venous congestion and vascular leakage in diabetic retinae. PMID:24789334

  10. Intraocular Pressure and Estimated Cerebrospinal Fluid Pressure. The Beijing Eye Study 2011

    PubMed Central

    You, Qi Sheng; Yang, Diya; Xie, Xiao Bin; Xu, Liang

    2014-01-01

    Purpose To examine a potential association between intraocular pressure (IOP) and cerebrospinal fluid pressure (CSFP) in a population-based setting. Methods The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years (range: 50–93 years). A detailed ophthalmic examination was performed. Based on a previous study with lumbar cerebrospinal fluid pressure (CSFP) measurements, CSFP was calculated as CSFP [mm Hg]?=?0.44×Body Mass Index [kg/m2]+0.16×Diastolic Blood Pressure [mm Hg]–0.18×Age [Years]. Results In multivariate analysis, IOP was associated with higher estimated CSFP (P<0.001; standardized correlation coefficient beta: 0.27; regression coefficient B: 0.20; 95% confidence interval (CI): 0.16, 0.24), after adjusting for thinner central corneal thickness (P<0.001; beta: 0.45; B: 0.04;95%CI: 0.04,0.04), smaller corneal curvature radius (P<0.001; beta:?0.11; B:?1.13;95%CI:?1.61,?0.64), shallower anterior chamber depth (P?=?0.01; beta:?0.05; B:?0.33;95%CI:?0.59,?0.08) and longer axial length (P?=?0.002; beta: 0.08; B: 0.20;95%CI: 0.08,0.32)), and after adjusting for the systemic parameters of higher pulse rate (P<0.001; beta: 0.08; B: 0.02;95%CI: 0.01,0.03), higher prevalence of arterial hypertension (P?=?0.002; beta: 0.06; B: 0.32;95%CI: 0.12,0.53)), frequency of drinking alcohol (P?=?0.02; beta: 0.04; B: 0.09;95%CI: 0.01,0.17), higher blood concentration of triglycerides (P?=?0.001; beta: 0.06; B: 0.06;95%CI: 0.02,0.10) and cholesterol (P?=?0.049; beta: 0.04; B: 0.08;95%CI: 0.00,0.17), and body mass index (P<0.001; beta:?0.13; B:?0.09;95%CI:?0.13,?0.06). In a parallel manner, estimated CSFP (mean: 10.8±3.7 mm Hg) was significantly associated with higher IOP (P<0.001; beta: 0.13; B: 0.18;95%CI: 0.13,0.23) after adjusting for rural region of habitation (P<0.001; beta:?0.37; B:?2.78;95%CI:?3.07,?2.48), higher systolic blood pressure (P<0.001; beta: 0.34; B: 0.06;95%CI: 0.05,0.07), higher pulse rate (P?=?0.003; beta: 0.05; B: 0.02;95%CI: 0.01,0.03), taller body height (P<0.001; beta: 0.11; B: 0.05;95%CI: 0.03,0.07), higher blood concentration of cholesterol (P?=?0.003; beta: 0.05; B: 0.17;95%CI: 0.06,0.28) and higher level of education (P?=?0.003; beta: 0.09; B: 0.30;95%CI: 0.16,0.45). Conclusions IOP was positively associated with estimated CSFP after adjusting for other ocular and systemic parameters. As a corollary, higher estimated CSFP was significantly associated with higher IOP in multivariate analysis. It fits with the notion that the arterial blood pressure, estimated CSFP and IOP are physiologically correlated with each other. PMID:25105777

  11. Genistein and other soya isoflavones are potent ligands for transthyretin in serum and cerebrospinal fluid.

    PubMed

    Radovi?, Branislav; Mentrup, Birgit; Köhrle, Josef

    2006-06-01

    Consumption of soya-based nutrients is increasing in modern society because of their potentially protective effects against chronic diseases. Soya products are also heavily advertised as alternative drugs for relief from symptoms of the menopause and for hormone replacement therapy. However, because of their oestrogenic activity, negative effects of isoflavones have been postulated. Therefore, we analysed influences of soya isoflavones, major soya constituents with endocrine activity, on thyroxine (T4) binding to its distribution proteins. Serum binding of (125)I-labelled L-T4 was analysed in the absence or presence of increasing concentrations of soya isoflavones using non-denaturing PAGE for analysis. Complete displacement of [(125)I]T4 binding to transthyretin (TTR) was observed in human serum incubated with genistein at concentrations >10 microM; interference started at >0.1 microM. Glycitein showed decreased and daidzein the lowest displacement potency. [(125)I]T4 was displaced to albumin in rat and to T4-binding globulin in human serum. Soya isoflavones also obstruct [(125)I]T4 binding to TTR in human cerebrospinal fluid (CSF). The inhibitory effect was confirmed in direct binding assays using purified TTR with 50% inhibitory concentration values of 0.07 microM for genistein, 0.2 microM for glycitein and 1.8 microM for daidzein. The present study underlined a potent competition of soya isoflavones for T4 binding to TTR in serum and CSF. Isoflavones might alter free thyroid hormone concentrations resulting in altered tissue availability and metabolism. As a consequence of this interference, one could expect a disturbance in the feedback regulation of hormonal networks, including the pituitary-thyroid-periphery axis during development and in adult organisms. PMID:16768841

  12. Cerebrospinal fluid inflammatory markers in patients with multiple sclerosis: a pilot study.

    PubMed

    Matej?íková, Z; Mareš, J; P?ikrylová Vranová, H; Klosová, J; Sládková, V; Doláková, J; Zapletalová, J; Ka?ovský, P

    2015-02-01

    Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Autoimmune inflammation is common in the early stages of MS. This stage is followed by the neurodegenerative process. The result of these changes is axon and myelin breakdown. Although MS is according to McDonald's revised diagnostic criteria primarily a clinical diagnosis, paraclinical investigation methods are an important part in the diagnosis of MS. In common practice, magnetic resonance imaging of the brain and spinal cord, examination of cerebrospinal fluid (CSF) and examination of visual evoked potentials are used. There are an increasing number of studies dealing with biomarkers in CSF and their role in the diagnosis and treatment of MS. We hypothesized that the levels of some markers could be changed in MS in comparison with controls. We studied five inflammatory markers [interleukin-6 (IL-6), interleukin-8, interleukin-10 (IL-10), beta-2-microglobulin, orosomucoid]. CSF and serum levels of inflammatory markers were assessed in 38 patients with newly diagnosed MS meeting McDonald's revised diagnostic criteria and in 28 subjects as a control group (CG). Levels of beta-2-microglobulin and interleukin-8 in CSF were found to be significantly higher in MS patients in comparison to CG (p < 0.001 resp. p = 0.007). No differences in other CSF markers (IL-6, IL-10 and orosomucoid) and serum levels of all markers between both groups were found. The levels of two studied inflammatory markers were found to be increased at the time of first clinical symptoms of MS. Research on the role of inflammatory and neurodegenerative markers in MS should continue. PMID:24894698

  13. Serum and cerebrospinal fluid profiles for syphilis in Thai patients with acute ischaemic stroke.

    PubMed

    Dharmasaroja, P A; Dharmasaroja, P

    2012-05-01

    The diagnosis of neurosyphilis is complicated in elderly patients who have cerebrovascular risk factors and present with ischaemic stroke. We performed an analysis of serum and cerebrospinal fluid (CSF) profiles for neurosyphilis in acute stroke patients, particularly in those with atherosclerotic risk factors. In sera, the rapid plasma reagin (RPR) test and Treponema pallidum haemagglutination assay (TPHA) were used. In CSF, the RPR and fluorescent treponemal antibody-absorption tests were used together with CSF white blood cell (WBC) count and protein level. Baseline characteristics, including atherosclerotic risk factors, severity of stroke and computed tomography brain scan images were collected. Of the total 284 patients, 24 (8.4%) had TPHA-positive sera, from which 29.2% had a positive CSF for syphilis. Seven stroke patients (2.5%), with a mean age of 65.7 years, were diagnosed with symptomatic neurosyphilis, and 71% of them had atherosclerotic risk factors. Most symptomatic patients (85.7%) had CSF WBCs>20 cells/mm(3), with a mean of 98.6 ± 136.0 versus 3.2 ± 7.3 in non-neurosyphilitic patients (P = 0.0009). Less than 50% of the symptomatic patients had CSF protein levels >50 mg/dL, and the protein levels of neurosyphilitic and non-neurosyphilitic groups were not significantly different, with means of 52.0 ± 12.9 and 51.8 ± 15.9 mg/dL, respectively. There were no significant differences in age and stroke severity. Interpretation of CSF findings, particularly of CSF WBC counts and protein levels, must be appropriate to ascertain true symptomatic neurosyphilis cases and to reduce false-positive diagnoses, particularly in countries with a high prevalence of T. pallidum infection. PMID:22648888

  14. Altered chemokine levels in the cerebrospinal fluid and plasma of suicide attempters.

    PubMed

    Janelidze, Shorena; Ventorp, Filip; Erhardt, Sophie; Hansson, Oskar; Minthon, Lennart; Flax, John; Samuelsson, Martin; Traskman-Bendz, Lil; Brundin, Lena

    2013-06-01

    Chemokines constitute a class of small inflammatory proteins that control the chemotaxis of leukocytes. They are also present in the central nervous system (CNS) and contribute to diverse physiological functions, such as the regulation of cell migration, axonal growth and neuronal survival. It is to date not known whether chemokines in the CNS are affected in psychiatric disorders. In this study, chemokine levels were measured in the cerebrospinal fluid (CSF) of 137 psychiatric patients in conjunction to a suicide attempt, and 43 healthy controls. A subgroup of patients (n = 42) was followed up with blood samples 12 years after the initial CSF collection, when they did not show suicidal behavior. The follow-up chemokine levels were compared to those of psychiatric patients (n = 17) who had never attempted suicide. Ultra-sensitive chemokine multiplex immunoassay was used to quantify eotaxin-1 (CCL11), interferon gamma-induced protein-10 (IP-10, CXCL10), macrophage inflammatory protein-1? (MIP-1?, CCL4), monocyte chemotactic protein-1 (MCP-1, CCL2), MCP-4 (CCL13) and thymus and activation regulated chemokine (TARC, CCL17). Patients were diagnosed using DSM-III-R/DSM-IV, and assessed using the Comprehensive Psychopathological Rating Scale (CPRS), including subscales, and the Suicidal Intent Scale (SIS). CSF eotaxin-1, MIP-1?, MCP-1, MCP-4 and TARC were significantly lower in suicide attempters than in healthy controls. Low chemokine levels were specifically associated with psychotic symptoms and pain. In the samples collected at follow-up, TARC was significantly lower in suicide attempters compared to psychiatric patients who had never attempted suicide. We also found a positive correlation between blood TARC and brain-derived neurotrophic factor (BDNF) levels. Our study thus provides evidence of reduced chemokine levels in suicide attempters, both in the acute suicidal setting, and at long-term, compared to non-attempters. These results warrant future studies on the detailed neurobiological functions of chemokines in psychiatric patients. PMID:23062672

  15. Glial and neuronal markers in cerebrospinal fluid predict progression in multiple sclerosis

    PubMed Central

    Olsson, Bob; Bau, Laura; Matas, Elisabet; Calvo, Álvaro Cobo; Andreasson, Ulf; Blennow, Kaj; Romero-Pinel, Lucia; Martínez-Yélamos, Sergio; Zetterberg, Henrik

    2015-01-01

    Objective: To investigate glial and neuronal biomarkers in cerebrospinal fluid (CSF) samples from patients with relapsing–remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS), and to evaluate their ability to predict conversion from CIS to clinically definite MS (CDMS) and also disability progression in MS. Methods: CSF levels of neurofilament light protein (NFL), t-tau, p-tau, glial fibrillary acidic protein (GFAP), S-100B, human chitinase 3-like 1 protein (YKL-40), monocyte chemoattractant protein-1 (MCP-1), ?-sAPP and ?-sAPP; and A?38, A?40 and A?42, were analyzed in 109 CIS patients and 192 RRMS patients. The mean follow-up time of these 301 patients was 11.7 ± 6.4 years. Results: High levels of NFL were associated with early conversion from CIS to CDMS (hazard ratio (HR) with 95% confidence interval (CI): 2.69 (1.75 – 4.15); p < 0.0001). High levels of YKL-40 and GFAP were associated with earlier progression in the Expanded Disability Status Scale (EDSS), score 3: YKL-40 (HR (95% CI): 2.78 (1.48 – 5.23); p = 0.001) and GFAP (HR (95% CI): 1.83 (1.01 – 3.35); p = 0.04). High levels of YKL-40 were associated with earlier progression to EDSS 6 (HR (95% CI): 4.57 (1.01 – 20.83); p = 0.05). Conclusions: CSF levels of NFL in CIS patients are an independent prognostic marker for conversion to CDMS. Whereas, CSF levels of YKL-40 and GFAP are independent prognostic markers for disability progression in MS. PMID:25732842

  16. Cerebrospinal fluid ??amyloid 1–42 concentration may predict cognitive decline in older women

    PubMed Central

    Gustafson, Deborah R; Skoog, Ingmar; Rosengren, Lars; Zetterberg, Henrik; Blennow, Kaj

    2007-01-01

    Background Low levels of cerebrospinal fluid (CSF) ??amyloid 1–42 (A?42) and high total tau (T?tau) are diagnostic for manifest Alzheimer's disease. It is not known, however, whether these biomarkers may be risk indicators for cognitive decline in otherwise healthy older people. Methods The longitudinal relationship between CSF markers, A?42 and T?tau, measured in 1992, and change in Mini?Mental State Examination (?MMSE) score between 1992 and 2002 were investigated in 55 women (aged 70–84?years, mean (SD) MMSE score?=?28.3 (1.5)), who were participants in the Prospective Population Study of Women in Gothenburg, Sweden. These women did not have dementia when they experienced lumbar puncture in 1992–3. Results Over the 8?year follow?up period, ?MMSE (range?=? +3 to ?21 points) was correlated with A?42 (Spearman's r?=?0.40, p?=?0.002), such that lower levels of A?42 were related to greater decline. This was also observed after excluding 4 women who developed dementia between 1992 and 2002 (Spearman's r?=?0.34, p?=?0.019). A multivariate logistic regression model predicting a decline of ?5 points on the MMSE (observed in six women), or a risk of developing dementia over the 8?year follow?up period (observed in four women), including age, education, A?42 and T?tau as covariates, showed that A?42 was the sole predictor of significant cognitive decline or dementia (OR per 100?pg/ml A?42?=?2.24, 95% CI 1.19 to 4.22, p?=?0.013). Conclusions Low levels of CSF A?42 may predict cognitive decline among older women without dementia. PMID:17098843

  17. Endostatin/Collagen XVIII Is Increased in Cerebrospinal Fluid after Severe Traumatic Brain Injury

    PubMed Central

    Chen, Hao; Xue, Li-Xia; Cao, He-Li; Chen, Shi-Wen; Guo, Yan; Gao, Wen-Wei; Ju, Shi-Ming; Tian, Heng-Li

    2013-01-01

    Recent studies have suggested that endogenous angiogenesis inhibitor endostatin/collagen XVIII might play an important role in the secondary brain injury following traumatic brain injury (TBI). In this study, we measured endostatin/collagen XVIII concentrations serially for 1 week after hospitalization by using the enzyme-linked immunosorbent assay method in the cerebrospinal fluid (CSF) of 30 patients with TBI and a Glasgow Coma Scale (GCS) score of 8 or less on admission. There was a significant trend toward increased CSF levels of endostatin after TBI versus control from 72?h after injury. In patients with GCS score of 3–5, CSF endostatin concentration was substantially higher at 72?h after injury than that in patients with GCS score of 6–8 (P < 0.05) and peaked rapidly at day 5 after injury, but decreased thereafter. The CSF endostatin concentration in 12 patients with an unfavorable outcome was significantly higher than that in 18 patients with a favorable outcome at day 5 (P = 0.043) and day 7 (P = 0.005) after trauma. Receiver operating characteristic curve analysis suggested a reliable operating point for the 7-day CSF endostatin concentration predicting poor prognosis to be 67.29?pg/mL. Our preliminary findings provide new evidence that endostatin/collagen XVIII concentration in the CSF increases substantially in patients with sTBI. Its dynamic change may have some clinical significance on the judgment of brain injury severity and the assessment of prognosis. This trial is registered with the ClinicalTrials.gov Identifier: NCT01846546. PMID:24089677

  18. Performance of laser bonded glass/polyimide microjoints in cerebrospinal fluid.

    PubMed

    Mian, A; Newaz, G; Georgiev, D G; Rahman, N; Vendra, L; Auner, G; Witte, R; Herfurth, H

    2007-03-01

    In this paper, laser bonded microjoints between glass and polyimide is considered to examine their potential applicability in encapsulating neural implants. To facilitate bonding between polyimide and glass, a thin titanium film with a thickness of 2 microm was deposited on borosilicate glass plates by a physical vapor deposition (PVD) process. Titanium coated glass was then joined with polyimide by using a cw fiber laser emitting at a wavelength of 1.1 microm (1.0 W) to prepare several tensile samples. Some of the samples were exposed to artificial cerebrospinal fluid (aCSF) at 37 degrees C for two weeks to assess long-term integrity of the joints. Both the as-received and aCSF soaked samples were subjected to uniaxial tensile loads for bond strengths measurements. The bond strengths for the as-received and aCSF soaked samples were measured to be 7.31 and 5.33 N/mm, respectively. Although the long-term exposure of the microjoints to aCSF has resulted in 26% reduction of bond strength, the samples still retain considerably high strength as compared with the titanium-polyimide samples. The failed glass/polyimide samples were also analyzed using optical microscopy, and failure mechanisms are discussed. In addition, a two dimensional finite element analysis (FEA) was conducted to understand the stress distribution within the substrate materials while the samples are in tension. The FEA results match reasonably well with the experimental load-displacement curves for as-received samples. Detailed discussion on various stress contours is presented in the paper, and the failure mechanisms observed from the experiment are shown in good agreement with the FEA predicted ones. PMID:17334691

  19. D-amino acid aberrations in cerebrospinal fluid and plasma of smokers.

    PubMed

    Luykx, Jurjen J; Bakker, Steven C; van Boxmeer, Loes; Vinkers, Christiaan H; Smeenk, Hanne E; Visser, Wouter F; Verhoeven-Duif, Nanda M; Strengman, Eric; Buizer-Voskamp, Jacobine E; de Groene, Lizzy; van Dongen, Eric Pa; Borgdorff, Paul; Bruins, Peter; de Koning, Tom J; Kahn, René S; Ophoff, Roel A

    2013-09-01

    The glutamatergic neurotransmission system and the N-methyl-D-aspartate receptor (NMDAR) have been implicated in smoking and alcohol consumption behavior. Preclinical studies have demonstrated that nicotine and ethanol influence NMDAR functionality, which may have a role in tendencies to consume these substances. Nonetheless, little is known about concentrations of NMDAR coagonists in the cerebrospinal fluid (CSF) and plasma of individuals who smoke or consume alcohol. Glycine and L- and D-stereoisomers of alanine, serine, and proline were therefore measured using ultra-high-performance liquid chromatography-tandem mass spectrometry in 403 healthy subjects. Nicotine and alcohol consumption were quantified using questionnaires. Possible differences in NMDAR coagonist concentrations in plasma and CSF were investigated using ANCOVA with age, body mass index, and storage duration as covariates. The significance threshold was Bonferroni corrected (?=0.00625). Compared with non-smokers, smokers displayed lower levels of D-proline in plasma (p=0.0027, Cohen's d=-0.41) and D-proline in CSF (p=0.0026, Cohen's d=-0.43). D-Serine in CSF was higher in smokers than in non-smokers (p=0.0052, Cohen's d=0.41). After subdividing participants based on smoking quantity, dose-dependent decreases were demonstrated in smokers for D-proline in plasma (F=5.65, p=0.0039) and D-proline in CSF (F=5.20, p=0.0060). No differences in NMDAR coagonist levels between alcohol consumption groups were detected. To our knowledge, this is the first report to implicate D-amino acids in smoking behavior of humans. Whether such concentration differences lie at the root of or result from smoking habits may be addressed in prospective studies. PMID:23615666

  20. Increased cerebrospinal fluid concentrations of asymmetric dimethylarginine correlate with adverse clinical outcome in subarachnoid hemorrhage patients.

    PubMed

    Li, Hua; Wu, Wei; Liu, Ming; Zhang, Xin; Zhang, Qing-Rong; Ni, Li; Hang, Chun-Hua

    2014-08-01

    Elevated cerebrospinal fluid (CSF) concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, have been found in patients with subarachnoid hemorrhage (SAH). In addition, CSF levels of ADMA are associated with the severity of vasospasm. However, the relation between CSF ADMA levels and the clinical outcome of SAH patients is still unclear. We hypothesized that elevated ADMA levels in CSF might be related to the clinical outcome of SAH patients. CSF ADMA levels were measured in 20 SAH patients at days 3-5, days 7-9 and days 12-14 after SAH onset using high-performance liquid chromatography. Cerebral vasospasm was assessed by transcranial Doppler ultra sonography. Clinical outcome at 2year follow-up was evaluated using the Karnofsky Performance Status scale (KPS). CSF ADMA concentrations in all SAH patients were significantly increased at days 3-5 (p=0.002) after SAH, peaked on days 7-9 (p<0.001) and remained elevated until days 12-14 (p<0.001). In subgroup analysis, significant increases of CSF ADMA levels were found in patients both with and without vasospasm. The KPS scores significantly correlated with CSF levels of ADMA at days 7-9 (correlation coefficient=-0.55, p=0.012; 95% confidence interval -0.80 to -0.14). Binary logistic regression analysis indicated that higher ADMA level at days 7-9 predicted a poor clinical outcome at 2year follow-up after SAH (odds ratio=1.722, p=0.039, 95% confidence interval 1.029 to 2.882). ADMA may be directly involved in the pathological process and future adverse prognosis of SAH. PMID:24814854

  1. Comprehensive immunophenotyping of cerebrospinal fluid cells in patients with neuroimmunological diseases.

    PubMed

    Han, Sungpil; Lin, Yen Chih; Wu, Tianxia; Salgado, Alan D; Mexhitaj, Ina; Wuest, Simone C; Romm, Elena; Ohayon, Joan; Goldbach-Mansky, Raphaela; Vanderver, Adeline; Marques, Adriana; Toro, Camilo; Williamson, Peter; Cortese, Irene; Bielekova, Bibiana

    2014-03-15

    We performed unbiased, comprehensive immunophenotyping of cerebrospinal fluid (CSF) and blood leukocytes in 221 subjects referred for the diagnostic work-up of neuroimmunological disorders to obtain insight about disease-specific phenotypes of intrathecal immune responses. Quantification of 14 different immune cell subsets, coupled with the assessment of their activation status, revealed physiological differences between intrathecal and systemic immunity, irrespective of final diagnosis. Our data are consistent with a model where the CNS shapes intrathecal immune responses to provide effective protection against persistent viral infections, especially by memory T cells, plasmacytoid dendritic cells, and CD56(bright) NK cells. Our data also argue that CSF immune cells do not simply reflect cells recruited from the periphery. Instead, they represent a mixture of cells that are recruited from the blood, have been activated intrathecally and leave the CNS after performing effector functions. Diagnosis-specific differences provide mechanistic insight into the disease process in the defined subtypes of multiple sclerosis (MS), neonatal onset multisystem inflammatory disease, and Aicardi-Goutières syndrome. This analysis also determined that secondary-progressive MS patients are immunologically closer to relapsing-remitting patients as compared with patients with primary-progressive MS. Because CSF immunophenotyping captures the biology of the intrathecal inflammatory processes, it has the potential to guide optimal selection of immunomodulatory therapies in individual patients and monitor their efficacy. Our study adds to the increasing number of publications that demonstrate poor correlation between systemic and intrathecal inflammatory biomarkers in patients with neuroimmunological diseases and stresses the importance of studying immune responses directly in the intrathecal compartment. PMID:24510966

  2. Lumbar nerve rootlet entrapment by an iatrogenically spliced percutaneous intra-thecal lumbar cerebrospinal fluid catheter

    PubMed Central

    Yue, James J.; Castro, Carlos A.; Scott, David

    2015-01-01

    Background Complications associated with the use of percutaneous intra-thecal lumbar indwelling spinal catheters include infection, hematoma, neurologic dysfunction, and persistent undesired retention among others. A case of iatrogenic splicing associated with neurologic dysfunction with the use of a percutaneous intra-thecal indwelling spinal catheter is presented in this study. Method Single case study review. Results Review of case materials indicate Y pattern splicing/fragmentation of an indwelling intra-thecal catheter causing neurologic dysfunction and resistance to removal during attempted removal. Pain and weakness were evident soon after insertion of the catheter and were amplified with attempted catheter removal. Computed tomography revealed a double dot sign on axial view and a Y appearance on sagittal view. Surgical findings revealed entrapment of nerve rootlets in the axilla of the spliced catheter. Conclusions Splicing/fragmentation causing neurologic dysfunction as well as catheter retention is described as a potential complication of intra-thecal indwelling cerebrospinal fluid catheters. A symptom of fragmentation of a catheter may include neurologic dysfunction including pain and weakness of a lumbar nerve root. If resistance is experienced upon attempted catheter removal, with or without associated neurologic dysfunction, further attempts at removal should not be attempted. In those cases in which pain and/or lumbar weakness are evident post catheter placement and/or following attempted removal, computed tomography should be performed. If fragmentation of a catheter is evident on CT scan, spinal surgical consultation should be obtained. Recommended spinal surgical intervention includes an open durotomy and visualization of catheter fragments and nerve rootlets and removal of catheter fragments. PMID:25600724

  3. Elevated levels of cerebrospinal fluid ?-synuclein oligomers in healthy asymptomatic LRRK2 mutation carriers

    PubMed Central

    Aasly, Jan O.; Johansen, Krisztina K.; Brønstad, Gunnar; Warø, Bjørg J.; Majbour, Nour K.; Varghese, Shiji; Alzahmi, Fatimah; Paleologou, Katerina E.; Amer, Dena A. M.; Al-Hayani, Abdulmonem; El-Agnaf, Omar M. A.

    2014-01-01

    Mutations in the leucine-rich repeat kinase 2 gene are the most common cause of autosomal dominant Parkinson’s disease (PD). To assess the cerebrospinal fluid (CSF) levels of ?-synuclein oligomers in symptomatic and asymptomatic leucine-rich repeat kinase 2 mutation carriers, we used enzyme-linked immunosorbent assays (ELISA) to investigate total and oligomeric forms of ?-synuclein in CSF samples. The CSF samples were collected from 33 Norwegian individuals with leucine-rich repeat kinase 2 mutations: 13 patients were clinically diagnosed with PD and 20 patients were healthy, asymptomatic leucine-rich repeat kinase 2 mutation carriers. We also included 35 patients with sporadic PD (sPD) and 42 age-matched healthy controls. Levels of CSF ?-synuclein oligomers were significantly elevated in healthy asymptomatic individuals carrying leucine-rich repeat kinase 2 mutations (n = 20; P < 0.0079) and in sPD group (n = 35; P < 0.003) relative to healthy controls. Increased ?-synuclein oligomers in asymptomatic leucine-rich repeat kinase 2 mutation carriers showed a sensitivity of 63.0% and a specificity of 74.0%, with an area under the curve of 0.66, and a sensitivity of 65.0% and a specificity of 83.0%, with an area under the curve of 0.74 for sPD cases. An inverse correlation between CSF levels of ?- synuclein oligomers and disease severity and duration was observed. Our study suggests that quantification of ?-synuclein oligomers in CSF has potential value as a tool for PD diagnosis and presymptomatic screening of high-risk individuals. PMID:25309429

  4. Cerebrospinal Fluid Secretory Ca2+-Dependent Phospholipase A2 Activity Is Increased in Alzheimer Disease

    PubMed Central

    Chalbot, Sonia; Zetterberg, Henrik; Blennow, Kaj; Fladby, Tormod; Grundke-Iqbal, Inge; Iqbal, Khalid

    2010-01-01

    BACKGROUND: The phospholipase A2 (PLA2) family comprises multiple isoenzymes that vary in their physicochemical properties, cellular localizations, calcium sensitivities, and substrate specificities. Despite these differences, PLA2s share the ability to catalyze the synthesis of the precursors of the proinflammatory mediators. To investigate the potential of PLA2 as a biomarker in screening neuroinflammatory disorders in both clinical and research settings, we developed a PLA2 assay and determined the predominant types of PLA2 activity in cerebrospinal fluid (CSF). METHODS: We used liposomes composed of a fluorescent probe (bis-Bodipy® FL C11-PC [1,2-bis-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-undecanoyl)-sn-glycero-3-phosphocholine]) and 1,2-dioleoyl-l-?-phosphatidylcholine as a substrate to measure CSF PLA2 activity in a 96-well microtiter plate format. We established the type of CSF PLA2 activity using type-specific inhibitors of PLA2. RESULTS: Using 5 ?L CSF per assay, our PLA2 activity assay was reproducible with CVs <15% in 2 CSF samples and for recombinant secretory Ca2+-dependent PLA2 (sPLA2) in concentrations ranging from 0.25 to 1 ?mol/L. This PLA2 assay allowed identification of sPLA2 activity in lumbar CSF from healthy individuals 20–77 years old that did not depend on either sex or age. Additionally, CSF sPLA2 activity was found to be increased (P = 0.0008) in patients with Alzheimer disease. CONCLUSIONS: Adult human CSF has sPLA2 activity that can be measured reliably with the assay described. This enzyme activity in the CSF is independent of both sex and age and might serve as a valuable biomarker of neuroinflammation, as we demonstrated in Alzheimer disease. PMID:19850632

  5. Cerebrospinal Fluid PKR Level Predicts Cognitive Decline in Alzheimer’s Disease

    PubMed Central

    Lapalus, Pauline; Prevot, Magali; Laplanche, Jean-Louis

    2013-01-01

    The cerebrospinal fluid (CSF) levels of the proapoptotic kinase R (PKR) and its phosphorylated PKR (pPKR) are increased in Alzheimer’s disease (AD), but whether CSF PKR concentrations are associated with cognitive decline in AD patients remain unknown. In this study, 41 consecutive patients with AD and 11 patients with amnestic mild cognitive impairment (aMCI) from our Memory Clinic were included. A lumbar puncture was performed during the following month of the clinical diagnosis and Mini-Mental State Examination (MMSE) evaluations were repeated every 6 months during a mean follow-up of 2 years. In AD patients, linear mixed models adjusted for age and sex were used to assess the cross-sectional and longitudinal associations between MMSE scores and baseline CSF levels of A? peptide (A? 1-42), Tau, phosphorylated Tau (p-Tau 181), PKR and pPKR. The mean (SD) MMSE at baseline was 20.5 (6.1) and MMSE scores declined over the follow-up (-0.12 point/month, standard error [SE]?=?0.03). A lower MMSE at baseline was associated with lower levels of CSF A? 1–42 and p-Tau 181/Tau ratio. pPKR level was associated with longitudinal MMSE changes over the follow-up, higher pPKR levels being related with an exacerbated cognitive deterioration. Other CSF biomarkers were not associated with MMSE changes over time. In aMCI patients, mean CSF biomarker levels were not different in patients who converted to AD from those who did not convert.These results suggest that at the time of AD diagnosis, a higher level of CSF pPKR can predict a faster rate of cognitive decline. PMID:23320095

  6. Specific absorbed fractions of energy from internal photon sources in brain tumor and cerebrospinal fluid

    SciTech Connect

    Evans, J.F. (Nuclear Engineering Program, Ohio State University, Columbus (Ohio (United States))); Stubbs, J.B. (Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee 37831-0117 (United States))

    1995-03-01

    Transferrin, radiolabeled with In-111, can be coinjected into glioblastoma multiforme lesions, and subsequent scintigraphic imaging can demonstrate the biokinetics of the cytotoxic transferrin. The administration of [sup 111]In transferrin into a brain tumor results in distribution of radioactivity in the brain, brain tumor, and the cerebrospinal fluid (CSF). Information about absorbed radiation doses to these regions, as well as other nearby tissues and organs, is important for evaluating radiation-related risks from this procedure. The radiation dose is usually estimated for a mathematical representation of the human body. We have included source/target regions for the eye, lens of the eye, spinal column, spinal CSF, cranial CSF, and a 100-g tumor within the brain of an adult male phantom developed by Cristy and Eckerman. The spinal column, spinal CSF, and the eyes have not been routinely included in photon transport simulations. Specific absorbed fractions (SAFs) as a function of photon energy were calculated using the ALGAMP computer code, which utilizes Monte Carlo techniques for simulating photon transport. The ALGAMP code was run three times, with the source activity distributed uniformly within the tumor, cranial CSF, and the spinal CSF volumes. These SAFs, which were generated for 12 discrete photon energies ranging from 0.01 to 4.0 MeV, were used with decay scheme data to calculate [ital S]-values needed for estimating absorbed doses. [ital S]-values for [sup 111]In are given for three source regions (brain tumor, cranial CSF, and spinal CSF) and all standard target regions/organs, the eye and lens, as well as to tissues within these source regions. [ital S]-values for the skeletal regions containing active marrow are estimated. These results are useful in evaluating the radiation doses from intracranial administration of [sup 111]In transferrin.

  7. Cerebrospinal fluid lysosomal enzymes and alpha-synuclein in Parkinson's disease.

    PubMed

    Parnetti, Lucilla; Chiasserini, Davide; Persichetti, Emanuele; Eusebi, Paolo; Varghese, Shiji; Qureshi, Mohammad M; Dardis, Andrea; Deganuto, Marta; De Carlo, Claudia; Castrioto, Anna; Balducci, Chiara; Paciotti, Silvia; Tambasco, Nicola; Bembi, Bruno; Bonanni, Laura; Onofrj, Marco; Rossi, Aroldo; Beccari, Tommaso; El-Agnaf, Omar; Calabresi, Paolo

    2014-07-01

    To assess the discriminating power of multiple cerebrospinal fluid (CSF) biomarkers for Parkinson's disease (PD), we measured several proteins playing an important role in the disease pathogenesis. The activities of ?-glucocerebrosidase and other lysosomal enzymes, together with total and oligomeric ?-synuclein, and total and phosphorylated tau, were thus assessed in CSF of 71 PD patients and compared to 45 neurological controls. Activities of ?-glucocerebrosidase, ?-mannosidase, ?-hexosaminidase, and ?-galactosidase were measured with established enzymatic assays, while ?-synuclein and tau biomarkers were evaluated with immunoassays. A subset of PD patients (n?=?44) was also screened for mutations in the ?-glucocerebrosidase-encoding gene (GBA1). In the PD group, ?-glucocerebrosidase activity was reduced (P?

  8. Development of a Cerebrospinal Fluid Lateral Reservoir Model in Rhesus Monkeys (Macaca mulatta).

    PubMed

    Lester McCully, Cynthia M; Bacher, John; MacAllister, Rhonda P; Steffen-Smith, Emilie A; Saleem, Kadharbatcha; Thomas, Marvin L; Cruz, Rafael; Warren, Katherine E

    2015-01-01

    Rapid, serial, and humane collection of cerebrospinal fluid (CSF) in nonhuman primates (NHP) is an essential element of numerous research studies and is currently accomplished via two different models. The CSF reservoir model (FR) combines a catheter in the 4th ventricle with a flexible silastic reservoir to permit circulating CSF flow. The CSF lateral port model (LP) consists of a lateral ventricular catheter and an IV port that provides static access to CSF and volume restrictions on sample collection. The FR model is associated with an intensive, prolonged recovery and frequent postsurgical hydrocephalus and nonpatency, whereas the LP model is associated with an easier recovery. To maximize the advantages of both systems, we developed the CSF lateral reservoir model (LR), which combines the beneficial features of the 2 previous models but avoids their limitations by using a reservoir for circulating CSF flow combined with catheter placement in the lateral ventricle. Nine adult male rhesus monkeys were utilized in this study. Pre-surgical MRI was performed to determine the coordinates of the lateral ventricle and location of choroid plexus (CP). The coordinates were determined to avoid the CP and major blood vessels. The predetermined coordinates were 100% accurate, according to MRI validation. The LR system functioned successfully in 67% of cases for 221 d, and 44% remain functional at 426 to 510 d postoperatively. Compared with established models, our LR model markedly reduced postoperative complications and recovery time. Development of the LR model was successful in rhesus macaques and is a useful alternative to the FR and LP methods of CSF collection from nonhuman primates. PMID:25730761

  9. Cerebrospinal fluid markers including trefoil factor 3 are associated with neurodegeneration in amyloid-positive individuals.

    PubMed

    Paterson, R W; Bartlett, J W; Blennow, K; Fox, N C; Shaw, L M; Trojanowski, J Q; Zetterberg, H; Schott, J M

    2014-01-01

    We aimed to identify cerebrospinal fluid (CSF) biomarkers associated with neurodegeneration in individuals with and without CSF evidence of Alzheimer pathology. We investigated 287 Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects (age=74.9±6.9; 22/48/30% with Alzheimer's disease/mild cognitive impairment/controls) with CSF multiplex analyte data and serial volumetric MRI. We calculated brain and hippocampal atrophy rates, ventricular expansion and Mini Mental State Examination decline. We used false discovery rate corrected regression analyses to assess associations between CSF variables and atrophy rates in individuals with and without amyloid pathology, adjusting in stages for tau, baseline volume, p-tau, age, sex, ApoE4 status and diagnosis. Analytes showing statistically significant independent relationships were entered into reverse stepwise analyses. Adjusting for tau, baseline volume, p-tau, age, sex and ApoE4, 4/83 analytes were significantly independently associated with brain atrophy rate, 1/83 with ventricular expansion and 2/83 with hippocampal atrophy. The strongest CSF predictor for the three atrophy measures was low trefoil factor 3 (TFF3). High cystatin C (CysC) was associated with higher whole brain atrophy and hippocampal atrophy rates. Lower levels of vascular endothelial growth factor and chromogranin A (CrA) were associated with higher whole brain atrophy. In exploratory reverse stepwise analyses, lower TFF3 was associated with higher rates of whole brain, hippocampal atrophy and ventricular expansion. Lower levels of CrA were associated with higher whole brain atrophy rate. The relationship between low TFF3 and increased hippocampal atrophy rate remained after adjustment for diagnosis. We identified a series of CSF markers that are independently associated with rate of neurodegeneration in amyloid-positive individuals. TFF3, a substrate for NOTCH processing may be an important biomarker of neurodegeneration across the Alzheimer spectrum. PMID:25072324

  10. Cerebrospinal fluid metabolomics reveals altered waste clearance and accelerated aging in HIV patients with neurocognitive impairment

    PubMed Central

    Cassol, Edana; Misra, Vikas; Dutta, Anupriya; Morgello, Susan; Gabuzda, Dana

    2014-01-01

    Objective(s): HIV-associated neurocognitive disorders (HAND) remain prevalent in HIV-infected patients on antiretroviral therapy (ART), but the underlying mechanisms are unclear. Some features of HAND resemble those of age-associated cognitive decline in the absence of HIV, suggesting that overlapping mechanisms may contribute to neurocognitive impairment. Design: Cross-sectional analysis of cerebrospinal fluid (CSF) from 100 individuals (46 HIV-positive patients and 54 HIV-negative controls). Methods: Untargeted CSF metabolite profiling was performed using liquid/gas chromatography followed by mass spectrometry. Cytokine profiling was performed by Bioplex. Bioinformatic analyses were performed in Metaboanalyst and R. Results: Alterations in the CSF metabolome of HIV patients on ART mapped to pathways associated with neurotransmitter production, mitochondrial function, oxidative stress, and metabolic waste. Many CSF metabolites altered in HIV overlapped with those altered with advanced age in HIV-negative controls, suggesting a pattern indicative of accelerated aging. Machine learning models identified neurotransmitters (glutamate, N-acetylaspartate), markers of glial activation (myo-inositol), and ketone bodies (beta-hydroxybutyric acid, 1,2-propanediol) as top-ranked classifiers of HAND. These CSF metabolites correlated with worse neurocognitive test scores, plasma inflammatory biomarkers [interferon (IFN)-?, IFN-?, interleukin (IL)-8, IL-1?, IL-6, IL-2Ra], and intrathecal IFN responses (IFN-? and kynurenine : tryptophan ratio), suggesting inter-relationships between systemic and intrathecal inflammation and metabolic alterations in CSF. Conclusions: Alterations in the CSF metabolome of HIV patients on ART suggest that persistent inflammation, glial responses, glutamate neurotoxicity, and altered brain waste disposal systems contribute to mechanisms involved in HAND that may be augmented with aging. PMID:24752083

  11. Analysis of Risk Factors and Management of Cerebrospinal Fluid Morbidity in the Treatment of Spinal Dysraphism

    PubMed Central

    Lee, Byung-Jou; Han, Seong-Rok; Choi, Chan-Young; Lee, Dong-Joon; Kang, Jae Heon

    2013-01-01

    Objective Spinal dysraphism defects span wide spectrum. Wound dehiscence is a common postoperative complication, and is a challenge in the current management of cerebrospinal fluid (CSF) leaks and wound healing. The purpose of this study is to evaluate the risks of CSF-related morbidity in the surgical treatment of spinal dysraphism. Methods Ten patients with spinal dysraphism were included in this retrospective study. The median age of the cohort was 4.8 months. To assess the risk of CSF morbidity, we measured the skin lesion area and the percentage of the skin lesion area relative to the back surface for each patient. We then analyzed the relationship between morbidity and the measured skin lesion area or related factors. Results The overall median skin lesion area was 36.2 cm2 (n=10). The percentage of the skin lesion area relative to the back surface ranged from 0.6% to 18.1%. During surgical reconstruction, 4 patients required subsequent operations to repair CSF morbidity. The comparison of the mean area of skin lesions between the CSF morbidity group and the non-CSF morbidity group was statistically significant (average volume skin lesion of 64.4±32.5 cm2 versus 27.7±27.8 cm2, p<0.05). CSF morbidity tended to occur either when the skin lesion area was up to 44.2 cm2 or there was preexisting fibrosis before revision with an accompanying broad-based dural defect. Conclusion Measuring the lesion area, including the skin, dura, and related surgical parameters, offers useful information for predicting wound challenges and selecting appropriate reconstructive surgery methods. PMID:24278652

  12. Idiopathic Normal Pressure Hydrocephalus has a Different Cerebrospinal Fluid Biomarker Profile from Alzheimer's Disease.

    PubMed

    Jingami, Naoto; Asada-Utsugi, Megumi; Uemura, Kengo; Noto, Rio; Takahashi, Makio; Ozaki, Akihiko; Kihara, Takeshi; Kageyama, Takashi; Takahashi, Ryosuke; Shimohama, Shun; Kinoshita, Ayae

    2015-01-01

    The diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is sometimes complicated by concomitant Alzheimer's disease (AD) pathology. The purpose of the present study is to identify an iNPH-specific cerebrospinal fluid (CSF) biomarker dynamics and to assess its ability to differentiate iNPH from AD. Total tau (t-tau), tau phosphorylated at threonine 181 (p-tau), amyloid-? (A?) 42 and 40, and leucine-rich ?-2-glycoprotein (LRG) were measured in 93 consecutive CSF samples consisting of 55 iNPH (46 tap test responders), 20 AD, 11 corticobasal syndrome, and 7 spinocerebeller disease. Levels of t-tau and p-tau were significantly decreased in iNPH patients especially in tap test responders compared to AD. Correlation was observed between Mini-Mental State Examination scores and A?42 in AD (R = 0.44) and mildly in iNPH (R = 0.28). Although A?42/40 ratio showed no significant difference between iNPH and AD (p = 0.08), the levels of A?40 and A?42 correlated positively with each other in iNPH (R = 0.73) but much less in AD (R = 0.26), suggesting that they have discrete amyloid clearance and pathology. LRG levels did not differ between the two. Thus, our study shows that although CSF biomarkers of iNPH patients can be affected by concomitant tau and/or amyloid pathology, CSF t-tau and p-tau are highly useful for differentiation of iNPH and AD. PMID:25428256

  13. Intracranial pressure pulse waveform correlates with aqueductal cerebrospinal fluid stroke volume

    PubMed Central

    Hamilton, Robert; Baldwin, Kevin; Fuller, Jennifer; Vespa, Paul; Hu, Xiao

    2012-01-01

    This study identifies a novel relationship between cerebrospinal fluid (CSF) stroke volume through the cerebral aqueduct and the characteristic peaks of the intracranial pulse (ICP) waveform. ICP waveform analysis has become much more advanced in recent years; however, clinical practice remains restricted to mean ICP, mainly due to the lack of physiological understanding of the ICP waveform. Therefore, the present study set out to shed some light on the physiological meaning of ICP morphological metrics derived by the morphological clustering and analysis of continuous intracranial pulse (MOCAIP) algorithm by investigating their relationships with a well defined physiological variable, i.e., the stroke volume of CSF through the cerebral aqueduct. Seven patients received both overnight ICP monitoring along with a phase-contrast MRI (PC-MRI) of the cerebral aqueduct to quantify aqueductal stroke volume (ASV). Waveform morphological analysis of the ICP signal was performed by the MOCAIP algorithm. Following extraction of morphological metrics from the ICP signal, nine temporal ICP metrics and two amplitude-based metrics were compared with the ASV via Spearman's rank correlation. Of the nine temporal metrics correlated with the ASV, only the width of the P2 region (ICP-Wi2) reached significance. Furthermore, both ICP pulse pressure amplitude and mean ICP did not reach significance. In this study, we showed the width of the second peak (ICP-Wi2) of an ICP pulse wave is positively related to the volume of CSF movement through the cerebral aqueduct. This finding is an initial step in bridging the gap between ICP waveform morphology research and clinical practice. PMID:22995390

  14. Intracranial pressure pulse waveform correlates with aqueductal cerebrospinal fluid stroke volume.

    PubMed

    Hamilton, Robert; Baldwin, Kevin; Fuller, Jennifer; Vespa, Paul; Hu, Xiao; Bergsneider, Marvin

    2012-11-01

    This study identifies a novel relationship between cerebrospinal fluid (CSF) stroke volume through the cerebral aqueduct and the characteristic peaks of the intracranial pulse (ICP) waveform. ICP waveform analysis has become much more advanced in recent years; however, clinical practice remains restricted to mean ICP, mainly due to the lack of physiological understanding of the ICP waveform. Therefore, the present study set out to shed some light on the physiological meaning of ICP morphological metrics derived by the morphological clustering and analysis of continuous intracranial pulse (MOCAIP) algorithm by investigating their relationships with a well defined physiological variable, i.e., the stroke volume of CSF through the cerebral aqueduct. Seven patients received both overnight ICP monitoring along with a phase-contrast MRI (PC-MRI) of the cerebral aqueduct to quantify aqueductal stroke volume (ASV). Waveform morphological analysis of the ICP signal was performed by the MOCAIP algorithm. Following extraction of morphological metrics from the ICP signal, nine temporal ICP metrics and two amplitude-based metrics were compared with the ASV via Spearman's rank correlation. Of the nine temporal metrics correlated with the ASV, only the width of the P2 region (ICP-Wi2) reached significance. Furthermore, both ICP pulse pressure amplitude and mean ICP did not reach significance. In this study, we showed the width of the second peak (ICP-Wi2) of an ICP pulse wave is positively related to the volume of CSF movement through the cerebral aqueduct. This finding is an initial step in bridging the gap between ICP waveform morphology research and clinical practice. PMID:22995390

  15. Biochemical, histological and functional correction of mucopolysaccharidosis Type IIIB by intra-cerebrospinal fluid gene therapy.

    PubMed

    Ribera, Albert; Haurigot, Virginia; Garcia, Miguel; Marcó, Sara; Motas, Sandra; Villacampa, Pilar; Maggioni, Luca; León, Xavier; Molas, Maria; Sánchez, Víctor; Muñoz, Sergio; Leborgne, Christian; Moll, Xavier; Pumarola, Martí; Mingozzi, Federico; Ruberte, Jesús; Añor, Sònia; Bosch, Fatima

    2015-04-01

    Gene therapy is an attractive tool for the treatment of monogenic disorders, in particular for lysosomal storage diseases (LSD) caused by deficiencies in secretable lysosomal enzymes in which neither full restoration of normal enzymatic activity nor transduction of all affected cells are necessary. However, some LSD such as Mucopolysaccharidosis Type IIIB (MPSIIIB) are challenging because the disease's main target organ is the brain and enzymes do not efficiently cross the blood-brain barrier even if present at very high concentration in circulation. To overcome these limitations, we delivered AAV9 vectors encoding for ?-N-acetylglucosaminidase (NAGLU) to the Cerebrospinal Fluid (CSF) of MPSIIIB mice with the disease already detectable at biochemical, histological and functional level. Restoration of enzymatic activity in Central Nervous System (CNS) resulted in normalization of glycosaminoglycan content and lysosomal physiology, resolved neuroinflammation and restored the pattern of gene expression in brain similar to that of healthy animals. Additionally, transduction of the liver due to passage of vectors to the circulation led to whole-body disease correction. Treated animals also showed reversal of behavioural deficits and extended lifespan. Importantly, when the levels of enzymatic activity were monitored in the CSF of dogs following administration of canine NAGLU-coding vectors to animals that were either naïve or had pre-existing immunity against AAV9, similar levels of activity were achieved, suggesting that CNS efficacy would not be compromised in patients seropositive for AAV9. Our studies provide a strong rationale for the clinical development of this novel therapeutic approach as the treatment for MPSIIIB. PMID:25524704

  16. The identification of irisin in human cerebrospinal fluid: influence of adiposity, metabolic markers, and gestational diabetes.

    PubMed

    Piya, Milan K; Harte, Alison L; Sivakumar, Kavitha; Tripathi, Gyanendra; Voyias, Philip D; James, Sean; Sabico, Shaun; Al-Daghri, Nasser M; Saravanan, Ponnusamy; Barber, Thomas M; Kumar, Sudhesh; Vatish, Manu; McTernan, Philip G

    2014-03-01

    Peripheral action of irisin improves glucose homeostasis and increases energy expenditure, with no data on a central role of irisin in metabolism. These studies sought to examine 1) presence of irisin in human cerebrospinal fluid (CSF) and banked human hypothalamic tissue, 2) serum irisin in maternal subjects across varying adiposities with or without gestational diabetes (GDM), and 3) their respective neonate offspring. CSF, serum, and neonatal cord serum were collected from 91 pregnant women with and without GDM attending for an elective cesarean section [body mass index (BMI): 37.7 ± 7.6 kg/m(2); age: 32 ± 8.3 yr]. Irisin was assessed by ELISA and correlated with biochemical and anthropometric data. Irisin expression was examined in human hypothalamus by immunohistochemical staining. Serum irisin in pregnant women was significantly lower in nonobese compared with obese and GDM subjects, after adjusting for BMI, lipids, and glucose. Irisin was present in neonatal cord serum (237 ± 8 ng/ml) and maternal CSF (32 ± 1.5 ng/ml). CSF irisin correlated positively with serum irisin levels from nonobese and obese pregnant women (P < 0.01), with CSF irisin significantly raised in GDM subjects (P < 0.05). Irisin was present in human hypothalamic sections in the paraventricular neurons, colocalized with neuropeptide Y. Irisin was detectable in CSF and in paraventricular neurons. Maternal serum irisin was lower in nonobese pregnant women after adjusting for BMI and a number of metabolic parameters. These studies indicate that irisin may have a central role in metabolism in addition to the known peripheral role. Further studies investigating the central action of irisin in human metabolic disease are required. PMID:24398403

  17. Pharmacokinetics of colistin in cerebrospinal fluid after intraventricular administration of colistin methanesulfonate.

    PubMed

    Imberti, Roberto; Cusato, Maria; Accetta, Giovanni; Marinò, Valeria; Procaccio, Francesco; Del Gaudio, Alfredo; Iotti, Giorgio A; Regazzi, Mario

    2012-08-01

    Intraventricular colistin, administered as colistin methanesulfonate (CMS), is the last resource for the treatment of central nervous system infections caused by panresistant Gram-negative bacteria. The doses and daily regimens vary considerably and are empirically chosen; the cerebrospinal fluid (CSF) pharmacokinetics of colistin after intraventricular administration of CMS has never been characterized. Nine patients (aged 18 to 73 years) were treated with intraventricular CMS (daily doses of 2.61 to 10.44 mg). Colistin concentrations were measured using a selective high-performance liquid chromatography (HPLC) assay. The population pharmacokinetics analysis was performed with the P-Pharm program. The pharmacokinetics of colistin could be best described by the one-compartment model. The estimated values (means ± standard deviations) of apparent CSF total clearance (CL/Fm, where Fm is the unknown fraction of CMS converted to colistin) and terminal half-life (t(1/2?)) were 0.033 ± 0.014 liter/h and 7.8 ± 3.2 h, respectively, and the average time to the peak concentration was 3.7 ± 0.9 h. A positive correlation between CL/Fm and the amount of CSF drained (range 40 to 300 ml) was observed. When CMS was administered at doses of ?5.22 mg/day, measured CSF concentrations of colistin were continuously above the MIC of 2 ?g/ml, and measured values of trough concentration (C(trough)) ranged between 2.0 and 9.7 ?g/ml. Microbiological cure was observed in 8/9 patients. Intraventricular administration of CMS at doses of ?5.22 mg per day was appropriate in our patients, but since external CSF efflux is variable and can influence the clearance of colistin and its concentrations in CSF, the daily dose of 10 mg suggested by the Infectious Diseases Society of America may be more prudent. PMID:22687507

  18. Proteomic Changes in Cerebrospinal Fluid of Presymptomatic and Affected Persons Carrying Familial Alzheimer Disease Mutations

    PubMed Central

    Ringman, John M.; Schulman, Howard; Becker, Chris; Jones, Ted; Bai, Yuchen; Immermann, Fred; Cole, Gregory; Sokolow, Sophie; Gylys, Karen; Geschwind, Daniel H.; Cummings, Jeffrey L.; Wan, Hong I.

    2013-01-01

    Objective To identify cerebrospinal fluid (CSF) protein changes in persons who will develop familial Alzheimer disease (FAD) due to PSEN1 and APP mutations, using unbiased proteomics. Design We compared proteomic profiles of CSF from individuals with FAD who were mutation carriers (MCs) and related noncarriers (NCs). Abundant proteins were depleted and samples were analyzed using liquid chromatography– electrospray ionization–mass spectrometry on a high-resolution time-of-flight instrument. Tryptic peptides were identified by tandem mass spectrometry. Proteins differing in concentration between the MCs and NCs were identified. Setting A tertiary dementia referral center and a proteomic biomarker discovery laboratory. Participants Fourteen FAD MCs (mean age, 34.2 years; 10 are asymptomatic, 12 have presenilin-1 [PSEN1] gene mutations, and 2 have amyloid precursor protein [APP] gene mutations) and 5 related NCs (mean age, 37.6 years). Results Fifty-six proteins were identified, represented by multiple tryptic peptides showing significant differences between MCs and NCs (46 upregulated and 10 downregulated); 40 of these proteins differed when the analysis was restricted to asymptomatic individuals. Fourteen proteins have been reported in prior proteomic studies in late-onset AD, including amyloid precursor protein, transferrin, ?1?-glycoprotein, complement components, afamin precursor, spondin 1, plasminogen, hemopexin, and neuronal pentraxin receptor. Many other proteins were unique to our study, including calsyntenin 3, AMPA (?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) 4 glutamate receptor, CD99 antigen, di-N-acetyl-chitobiase, and secreted phosphoprotein 1. Conclusions We found much overlap in CSF protein changes between individuals with presymptomatic and symptomatic FAD and those with late-onset AD. Our results are consistent with inflammation and synaptic loss early in FAD and suggest new presymptomatic biomarkers of potential usefulness in drug development. PMID:22232349

  19. Aquaporin-4 expression in the cerebrospinal fluid in congenital human hydrocephalus

    PubMed Central

    2013-01-01

    Background Aquaporin-4 (AQP4) is a water channel mainly located in the ventricular ependymal cells (brain-CSF barrier), the sub-ependymal glia, glia limitans and in end-feet of astrocytes in at the blood–brain barrier (BBB). Methods In the present work, the expression of AQP4 in the cerebrospinal fluid (CSF) in control and congenital human hydrocephalus infants (obstructive and communicating), was analysed by Western-blot and enzyme immunoassay (ELISA). Results AQP4 was found to be high compared to the control in the CSF in congenital hydrocephalus patients. Western-blot showed higher values for AQP4 than controls in communicating hydrocephalus (communicating: 38.3%, control: 6.9% p?

  20. Alterations of endocannabinoids in cerebrospinal fluid of dogs with epileptic seizure disorder

    PubMed Central

    2013-01-01

    Background Epilepsy is one of the most common chronic neurological disorders in dogs characterized by recurrent seizures. The endocannabinoid (EC) system plays a central role in suppressing pathologic neuronal excitability and in controlling the spread of activity in an epileptic network. Endocannabinoids are released on demand and their dysregulation has been described in several pathological conditions. Recurrent seizures may lead to an adverse reorganization of the EC system and impairment of its protective effect. In the current study, we tested the hypothesis that cerebrospinal fluid (CSF) concentrations of the endocannabinoids anandamide (AEA) and 2-arachidonoyl glycerol (2AG) are altered in epileptic dogs. Concentrations of AEA and total AG (sum of 2AG and 1AG) were measured in 40 dogs with idiopathic epilepsy and in 16 unaffected, healthy control dogs using liquid chromatography combined with tandem mass spectrometry. Results AEA and total AG were measured at 4.94 (3.18 – 9.17) pM and 1.43 (0.90 – 1.92) nM in epileptic dogs and at 3.19 (2.04 – 4.28) pM and 1.76 (1.08 – 2.69) nM in the control group, respectively (median, 25 – 75% percentiles in brackets). The AEA difference between epileptic and healthy dogs was statistically significant (p

  1. Increased Interleukin-17 in Peripheral Blood and Cerebrospinal Fluid of Neurosyphilis Patients

    PubMed Central

    Wang, Cuini; Zhu, Lin; Gao, Zixiao; Guan, Zhifang; Lu, Haikong; Shi, Mei; Gao, Ying; Xu, Huanbin; Yang, X. Frank; Zhou, Pingyu

    2014-01-01

    Background Treponema pallidum infection evokes vigorous immune responses, resulting in tissue damage. Several studies have demonstrated that IL-17 may be involved in the pathogenesis of syphilis. However, the role of Th17 response in neurosyphilis remains unclear. Methodology/Principal Findings In this study, Th17 in peripheral blood from 103 neurosyphilis patients, 69 syphilis patients without neurological involvement, and 70 healthy donors were analyzed by flow cytometry. The level of IL-17 in cerebrospinal fluid (CSF) was quantified by ELISA. One-year follow up for 44 neurosyphilis patients was further monitored to investigate the role of Th17/IL-17 in neurosyphilis. We found that the frequency of Th17 cells was significantly increased in peripheral blood of patients with neurosyphilis, in comparison to healthy donors. IL-17 in CSF were detected from 55.3% neurosyphilis patients (in average of 2.29 (0–59.83) pg/ml), especially in those with symptomatic neurosyphilis (61.9%). CSF IL-17 was predominantly derived from Th17 cells in neurosyphilis patients. Levels of IL-17 in CSF of neurosyphilis patients were positively associated with total CSF protein levels and CSF VDRL (Venereal Disease Research Laboratory) titers. Notably, neurosyphilis patients with undetectable CSF IL-17 were more likely to confer to CSF VDRL negative after treatment. Conclusions These findings indicate that Th17 response may be involved in central nervous system damage and associated with clinical symptoms in neurosyphilis patients. Th17/IL-17 may be used as an alternative surrogate marker for assessing the efficacy of clinical treatment of neurosyphilis patients. PMID:25080350

  2. Increased ?-synuclein levels in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease.

    PubMed

    Kasai, Takashi; Tokuda, Takahiko; Ishii, Ryotaro; Ishigami, Noriko; Tsuboi, Yoshio; Nakagawa, Masanori; Mizuno, Toshiki; El-Agnaf, Omar M A

    2014-06-01

    Recent studies have shown that cerebrospinal fluid (CSF) levels of ?-synuclein (?-syn) are highly elevated in patients with Creutzfeldt-Jakob disease (CJD) compared to controls. However, the diagnostic value of CSF ?-syn in CJD has not been established. To confirm whether CSF ?-syn is increased in CJD and is a useful marker for this disease, two independent enzyme-linked immunoabsorbent assays (ELISAs) specific for ?-syn were used: ELISA 211-FL140, which is specific for full-length ?-syn, and ELISA N19-FL140, which is specific for the full-length and associated C-terminal truncated forms of ?-syn. CSF samples from 24 patients with CJD and 24 controls were assessed in this study. We found that samples from the CJD patients showed significantly higher levels of CSF ?-syn compared to controls in both ELISA (211-FL140 or N19-FL140) tests (P = 0.0467 and P = 0.0010, respectively). However, there was a considerable overlap in the concentration ranges of the two groups of subjects. We also measured the levels of total tau (t-tau) protein in these samples and found that CSF t-tau levels were 5-10-times higher in the CJD group (P < 0.0001) compared with the controls. When the CSF t-tau and ?-syn levels were combined, the area under the ROC curve (AUC) was slightly increased in clinically diagnosed CJD cases (AUC of 0.964) relative to an AUC of 0.943 for increased CSF t-tau alone. The combined use of CSF ?-syn and t-tau levels may be a useful biomarker for the diagnosis of CJD. PMID:24737170

  3. Proteomic analysis of the cerebrospinal fluid of patients with restless legs syndrome/Willis-Ekbom disease

    PubMed Central

    2013-01-01

    Background Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED) is a sensorimotor disorder that causes patients to experience overwhelming and distressing sensations in the legs compelling the patient to move their legs to provide relief. The purpose of this study was to determine if biomarkers in the cerebrospinal fluid can distinguish RLS/WED patients from neurological controls. Methods We obtained CSF samples by lumbar puncture from 5 early-onset RLS/WED patients and 5 controls. We performed 2-dimensional difference in-gel electrophoresis (2D-DIGE). Proteins that were significantly altered were identified by Student’s t-test. Protein spots that were differentially expressed (p ? 0.05, Av. Ratio ? 2.0) between RLS/WED and control CSF samples were identified using MALDI-TOF-MS. Statistical analyses of the validation immunoblot assays were performed using Student’s t-test. Results In this discovery study we identified 6 candidate CSF protein markers for early-onset RLS/WED. Four proteins (Cystatin C, Lipocalin-type Prostaglandin D2 Synthase, Vitamin D binding Protein, and ?-Hemoglobin) were increased and 2 proteins (Apolipoprotein A1 and ?-1-acid Glycoprotein) were decreased in RLS/WED patients. Conclusions Our results reveal a protein profile in the RLS/WED CSF that is consistent with clinical findings of disruptive sleep, cardiovascular dysfunction and painful symptoms. Moreover, protein profiles are consistent with neuropathological findings of activation of hypoxia inducible factor (HIF) pathways and alterations in dopaminergic systems. These data indicate the CSF of RLS/WED patients may provide information relevant to biological basis for RLS/WED, treatment strategies and potential new treatment targets. PMID:23758918

  4. Protein analysis in human cerebrospinal fluid: Physiological aspects, current progress and future challenges.

    PubMed

    Hühmer, Andreas F; Biringer, Roger G; Amato, Heidi; Fonteh, Alfred N; Harrington, Michael G

    2006-01-01

    The introduction of lumbar puncture into clinical medicine over 100 years ago marks the beginning of the study of central nervous system diseases using the human cerebrospinal fluid (CSF). Ever since, CSF has been analyzed extensively to elucidate the physiological and biochemical bases of neurological disease. The proximity of CSF to the brain makes it a good target for studying the pathophysiology of brain functions, but the barrier function of the CSF also impedes its diagnostic value. Today, measurements to determine alterations in the composition of CSF are central in the differential diagnosis of specific diseases of the central nervous system (CNS). In particular, the analysis of the CSF protein composition provides crucial information in the diagnosis of CNS diseases. This enables the assessment of the physiology of the blood-CSF barrier and of the immunology of intrathecial responses. Besides those routine measurements, protein compositional studies of CSF have been extended recently to many other proteins in the expectation that comprehensive analysis of lower abundance CSF proteins will lead to the discovery of new disease markers. Disease marker discovery by molecular profiling of the CSF tissue has the enormous potential of providing many new disease relevant molecules. New developments in protein profiling techniques hold promise for the discovery and validation of relevant disease markers. In this review, we summarize the current efforts and progress in CSF protein profiling measurements using conventional and current protein analysis tools. We also discuss necessary development in methodology in order to have the highest impact on the study of the molecular composition of CSF proteins. PMID:16410649

  5. Reduced Levels of Nitric Oxide Metabolites in Cerebrospinal Fluid Are Associated with Equine Protozoal Myeloencephalitis

    PubMed Central

    Njoku, Chinedu J.; Saville, William J. A.; Reed, Stephen M.; Oglesbee, Michael J.; Rajala-Schultz, Päivi J.; Stich, Roger W.

    2002-01-01

    Equine protozoal myeloencephalitis (EPM) is a disease of horses that is primarily associated with infection with the apicomplexan Sarcocystis neurona. Infection with this parasite alone is not sufficient to induce the disease, and the mechanism of neuropathogenesis associated with EPM has not been reported. Nitric oxide (NO) functions as a neurotransmitter, a vasodilator, and an immune effector and is produced in response to several parasitic protozoa. The purpose of this work was to determine if the concentration of NO metabolites (NOx?) in the cerebrospinal fluid (CSF) is correlated with the development of EPM. CSF NOx? levels were measured before and after transport-stressed, acclimated, or dexamethasone-treated horses (n = 3 per group) were experimentally infected with S. neurona sporocysts. CSF NOx? levels were also compared between horses that were diagnosed with EPM after natural infection with S. neurona and horses that did not have clinical signs of disease or that showed no evidence of infection with the parasite (n = 105). Among the experimentally infected animals, the mean CSF NOx? levels of the transport-stressed group, which had the most severe clinical signs, was reduced after infection, while these values were found to increase after infection in the remaining groups that had less severe signs of EPM. Under natural conditions, horses with EPM (n = 65) had a lower mean CSF NOx? concentration than clinically normal horses with antibodies (Abs) against S. neurona (n = 15) in CSF, and horses that developed ataxia (n = 81) had a significantly lower mean CSF NOx? concentration than horses that did not have neurologic signs (n = 24). In conclusion, lower CSF NOx? levels were associated with clinical EPM, suggesting that measurement of CSF NOx? levels could improve the accuracy of diagnostic tests that are based upon detection of S. neurona-specific Abs in CSF alone and that reduced NO levels could be causatively related to the development of EPM. PMID:11986267

  6. Reduced levels of nitric oxide metabolites in cerebrospinal fluid are associated with equine protozoal myeloencephalitis.

    PubMed

    Njoku, Chinedu J; Saville, William J A; Reed, Stephen M; Oglesbee, Michael J; Rajala-Schultz, Päivi J; Stich, Roger W

    2002-05-01

    Equine protozoal myeloencephalitis (EPM) is a disease of horses that is primarily associated with infection with the apicomplexan Sarcocystis neurona. Infection with this parasite alone is not sufficient to induce the disease, and the mechanism of neuropathogenesis associated with EPM has not been reported. Nitric oxide (NO) functions as a neurotransmitter, a vasodilator, and an immune effector and is produced in response to several parasitic protozoa. The purpose of this work was to determine if the concentration of NO metabolites (NO(x)(-)) in the cerebrospinal fluid (CSF) is correlated with the development of EPM. CSF NO(x)(-) levels were measured before and after transport-stressed, acclimated, or dexamethasone-treated horses (n = 3 per group) were experimentally infected with S. neurona sporocysts. CSF NO(x)(-) levels were also compared between horses that were diagnosed with EPM after natural infection with S. neurona and horses that did not have clinical signs of disease or that showed no evidence of infection with the parasite (n = 105). Among the experimentally infected animals, the mean CSF NO(x)(-) levels of the transport-stressed group, which had the most severe clinical signs, was reduced after infection, while these values were found to increase after infection in the remaining groups that had less severe signs of EPM. Under natural conditions, horses with EPM (n = 65) had a lower mean CSF NO(x)(-) concentration than clinically normal horses with antibodies (Abs) against S. neurona (n = 15) in CSF, and horses that developed ataxia (n = 81) had a significantly lower mean CSF NO(x)(-) concentration than horses that did not have neurologic signs (n = 24). In conclusion, lower CSF NO(x)(-) levels were associated with clinical EPM, suggesting that measurement of CSF NO(x)(-) levels could improve the accuracy of diagnostic tests that are based upon detection of S. neurona-specific Abs in CSF alone and that reduced NO levels could be causally related to the development of EPM. PMID:11986267

  7. Features of the Sinushunt® and its influence on the cerebrospinal fluid system

    PubMed Central

    Eklund, A; Koskinen, L; Malm, J

    2004-01-01

    Objectives: A new cerebrospinal fluid (CSF) shunt system, Sinushunt®, has recently been introduced. CSF is shunted from the ventricles to the transverse sinus. The Sinushunt is not a classical differential pressure shunt; instead, it opens as soon as there is a positive pressure over the shunt and the flow is dependent on the resistance of the system, which is high compared with traditional CSF shunts. The objective of this study was to characterise the features of the Sinushunt and to evaluate its influence on the CSF system. Methods: Five brand new Sinushunts with distal catheters were tested. An automated, computerised experimental apparatus based on regulation of pressure, built into an incubator at 37 °C, was used. Opening pressure, resistance, and anti-reflux properties were determined. Results: The mean (SD) opening pressure was highly dependent on the pressure in the sinus: Popen = 1.3 (0.6) mm Hg with Psinus = 0.0 mm Hg, and Popen = 7.5 (0.6) mm Hg for Psinus = 6.5 mm Hg. The mean (SD) resistance of the shunts was 7.9 (0.3) mm Hg/ml/min and not clinically significantly affected by the sinus pressure. In one shunt there was reflux, and in another two shunts there was a very small, but similar, tendency. Conclusions: This study confirms that the resistance of the Sinushunt is comparable to the physiological values in humans. However, the optimal post-operative resistance for different hydrocephalus types is unknown, and randomised clinical trials are needed to confirm improved outcome and reduced complication rate for the Sinushunt compared with traditional low resistance ventriculoperitoneal shunts. A weakness of the anti-reflux system of the Sinushunt must be suspected and has to be further investigated. PMID:15258219

  8. SNPs associated with cerebrospinal fluid phospho-tau levels influence rate of decline in Alzheimer's disease.

    PubMed

    Cruchaga, Carlos; Kauwe, John S K; Mayo, Kevin; Spiegel, Noah; Bertelsen, Sarah; Nowotny, Petra; Shah, Aarti R; Abraham, Richard; Hollingworth, Paul; Harold, Denise; Owen, Michael M; Williams, Julie; Lovestone, Simon; Peskind, Elaine R; Li, Ge; Leverenz, James B; Galasko, Douglas; Morris, John C; Fagan, Anne M; Holtzman, David M; Goate, Alison M

    2010-09-01

    Alzheimer's Disease (AD) is a complex and multifactorial disease. While large genome-wide association studies have had some success in identifying novel genetic risk factors for AD, case-control studies are less likely to uncover genetic factors that influence progression of disease. An alternative approach to identifying genetic risk for AD is the use of quantitative traits or endophenotypes. The use of endophenotypes has proven to be an effective strategy, implicating genetic risk factors in several diseases, including anemia, osteoporosis and heart disease. In this study we identify a genetic factor associated with the rate of decline in AD patients and present a methodology for identification of other such factors. We have used an established biomarker for AD, cerebrospinal fluid (CSF) tau phosphorylated at threonine 181 (ptau(181)) levels as an endophenotype for AD, identifying a SNP, rs1868402, in the gene encoding the regulatory sub-unit of protein phosphatase B, associated with CSF ptau(181) levels in two independent CSF series (P(combined) = 1.17 x 10(-05)). We show no association of rs1868402 with risk for AD or age at onset, but detected a very significant association with rate of progression of disease that is consistent in two independent series (P(combined) = 1.17 x 10(-05)). Our analyses suggest that genetic variants associated with CSF ptau(181) levels may have a greater impact on rate of progression, while genetic variants such as APOE4, that are associated with CSF A?(42) levels influence risk and onset but not the rate of progression. Our results also suggest that drugs that inhibit or decrease tau phosphorylation may slow cognitive decline in individuals with very mild dementia or delay the appearance of memory problems in elderly individuals with low CSF A?(42) levels. Finally, we believe genome-wide association studies of CSF tau/ptau(181) levels should identify novel genetic variants which will likely influence rate of progression of AD. PMID:20862329

  9. Cerebrospinal fluid APOE levels: an endophenotype for genetic studies for Alzheimer's disease

    PubMed Central

    Cruchaga, Carlos; Kauwe, John S.K.; Nowotny, Petra; Bales, Kelly; Pickering, Eve H.; Mayo, Kevin; Bertelsen, Sarah; Hinrichs, Anthony; Fagan, Anne M.; Holtzman, David M.; Morris, John C.; Goate, Alison M.

    2012-01-01

    The apolipoprotein E (APOE) genotype is the major genetic risk factor for Alzheimer's disease (AD). We have access to cerebrospinal fluid (CSF) and plasma APOE protein levels from 641 individuals and genome-wide genotyped data from 570 of these samples. The aim of this study was to test whether CSF or plasma APOE levels could be a useful endophenotype for AD and to identify genetic variants associated with APOE levels. We found that CSF (P = 8.15 × 10?4) but not plasma (P = 0.071) APOE protein levels are significantly associated with CSF A?42 levels. We used Mendelian randomization and genetic variants as instrumental variables to confirm that the association of CSF APOE with CSF A?42 levels and clinical dementia rating (CDR) is not because of a reverse causation or confounding effect. In addition the association of CSF APOE with A?42 levels was independent of the APOE ?4 genotype, suggesting that APOE levels in CSF may be a useful endophenotype for AD. We performed a genome-wide association study to identify genetic variants associated with CSF APOE levels: the APOE ?4 genotype was the strongest single-genetic factor associated with CSF APOE protein levels (P = 6.9 × 10?13). In aggregate, the Illumina chip single nucleotide polymorphisms explain 72% of the variability in CSF APOE protein levels, whereas the APOE ?4 genotype alone explains 8% of the variability. No other genetic variant reached the genome-wide significance threshold, but nine additional variants exhibited a P-value <10?6. Pathway mining analysis indicated that these nine additional loci are involved in lipid metabolism (P = 4.49 × 10?9). PMID:22821396

  10. Cerebrospinal fluid APOE levels: an endophenotype for genetic studies for Alzheimer's disease.

    PubMed

    Cruchaga, Carlos; Kauwe, John S K; Nowotny, Petra; Bales, Kelly; Pickering, Eve H; Mayo, Kevin; Bertelsen, Sarah; Hinrichs, Anthony; Fagan, Anne M; Holtzman, David M; Morris, John C; Goate, Alison M

    2012-10-15

    The apolipoprotein E (APOE) genotype is the major genetic risk factor for Alzheimer's disease (AD). We have access to cerebrospinal fluid (CSF) and plasma APOE protein levels from 641 individuals and genome-wide genotyped data from 570 of these samples. The aim of this study was to test whether CSF or plasma APOE levels could be a useful endophenotype for AD and to identify genetic variants associated with APOE levels. We found that CSF (P = 8.15 × 10(-4)) but not plasma (P = 0.071) APOE protein levels are significantly associated with CSF A?(42) levels. We used Mendelian randomization and genetic variants as instrumental variables to confirm that the association of CSF APOE with CSF A?(42) levels and clinical dementia rating (CDR) is not because of a reverse causation or confounding effect. In addition the association of CSF APOE with A?(42) levels was independent of the APOE ?4 genotype, suggesting that APOE levels in CSF may be a useful endophenotype for AD. We performed a genome-wide association study to identify genetic variants associated with CSF APOE levels: the APOE ?4 genotype was the strongest single-genetic factor associated with CSF APOE protein levels (P = 6.9 × 10(-13)). In aggregate, the Illumina chip single nucleotide polymorphisms explain 72% of the variability in CSF APOE protein levels, whereas the APOE ?4 genotype alone explains 8% of the variability. No other genetic variant reached the genome-wide significance threshold, but nine additional variants exhibited a P-value <10(-6). Pathway mining analysis indicated that these nine additional loci are involved in lipid metabolism (P = 4.49 × 10(-9)). PMID:22821396

  11. Melatonin from cerebrospinal fluid but not from blood reaches sheep cerebral tissues under physiological conditions.

    PubMed

    Legros, C; Chesneau, D; Boutin, J A; Barc, C; Malpaux, B

    2014-03-01

    The pineal gland secretes melatonin (MLT) that circulates in the blood and cerebrospinal fluid (CSF). We provide data to support the hypothesis that, in sheep and possibly in humans, only the CSF MLT, and not the blood MLT, can provide most of MLT to the cerebral tissue in high concentrations, particularly in the periventricular area. The MLT content of sheep brain, our chosen animal model, was found in significant concentration gradients oriented from the ventricle (close to the CSF) to the cerebral tissue, with concentrations varying by a factor of 1-125. The highest concentrations were observed close to the ventricle wall, whereas the lowest concentrations were furthest from the ventricles (407.0 ± 71.5 pg/ml compared to 84.7 ± 5.2 pg/ml around the third ventricle). This concentration gradient was measured in brain tissue collected at mid-day and at the end of the night. Nocturnal concentrations were higher than daytime concentrations, reflecting the diurnal variation in the pineal gland. The concentration gradient was not detected when MLT was delivered to the brain via the bloodstream. The diffusion of MLT to cerebral tissues via CSF was supported by in vivo scintigraphy and autoradiography. 2-[(123)I]-MLT infused into the CSF quickly and efficiently diffused into the brain tissues, whereas [(123)I]-iodine (control) was mostly washed away by the CSF flow and [(123)I]-bovine serum albumin remained mostly in the CSF. Taken together, these data support a critical role of CSF in providing the brain with MLT. PMID:24460899

  12. Proteomic analysis of cerebrospinal fluid in Alzheimer's disease: wanted dead or alive.

    PubMed

    Oláh, Zita; Kálmán, János; Tóth, Melinda E; Zvara, Ágnes; Sántha, Miklós; Ivitz, Eszter; Janka, Zoltán; Pákáski, Magdolna

    2015-01-01

    Clinical diagnosis of Alzheimer's disease (AD) relying on symptomatic features has a low specificity, emphasizing the importance of the pragmatic use of neurochemical biomarkers. The most advanced and reliable markers are amyloid-? (A?42), total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) with relatively high levels of sensitivity, specificity, and diagnostic accuracy. Recent advances within the field of proteomics offer the potential to search for novel biomarkers in CSF by using modern methods, such as microarrays. The purpose of this study was to identify pathognostic proteins in CSF obtained from patients whose clinical AD diagnosis was confirmed by the "core" biomarkers. CSF samples were obtained from 25 AD patients and 25 control individuals. The levels of A?42, t-tau, and p-tau were measured by ELISA. In the microarray experiments, ultrasensitive slides representing of 653 antigens were used. Apolipoprotein E genotyping was also determined. A decrease of seven CSF proteins in AD were found, four of them (POLG, MGMT, parkin, and ApoD) have a protective function against neuronal death, while the remaining three proteins (PAR-4, granzyme B, Cdk5) trigger multiple pathways facilitating neuronal cell death. Since these proteins from CSF samples could not be identified by western blot, their decreased levels in AD patients were not verified. Our results provide new information of pathognostic importance of POLG and granzyme B in AD. Although the function of MGMT, parkin, ApoD, PAR-4, and Cdk5 was previously known in AD, the findings presented here provide novel evidence of the significance of CSF analysis in the mapping of the AD pathomechanism. PMID:25428253

  13. Neuropharmacokinetics of two investigational compounds in rats: divergent temporal profiles in the brain and cerebrospinal fluid.

    PubMed

    Tang, Cuyue; Chen, Ting; Kapadnis, Sudarshan; Hodgdon, Hilliary; Tao, Yi; Chen, Xing; Wen, Melody; Costa, Don; Murphy, Deirdre; Nolan, Scott; Flood, Dorothy G; Welty, Devin F; Koenig, Gerhard

    2014-10-15

    Two investigational compounds (FRM-1, (R)-7-fluoro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide and FRM-2, (R)-7-cyano-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide) resided in rat brain longer than in systemic circulation. In Caco-2 directional transport studies, they both showed good intrinsic passive permeability but differed significantly in efflux susceptibility (efflux ratio of <2 and ?7, respectively), largely attributed to P-glycoprotein (P-gp). Capitalizing on these interesting properties, we investigated how cerebrospinal fluid (CSF) concentration (CCSF) would be shaped by unbound plasma concentration (Cu,p) and unbound brain concentration (Cu,b) in disequilibrium conditions and at steady state. Following subcutaneous administration, FRM-1CCSF largely followed Cu,p initially and leveled between Cu,p and Cu,b. However, it gradually approached Cu,b and became lower than, but parallel to Cu,b at the terminal phase. In contrast, FRM-2CCSF temporal profile mostly paralleled the Cu,p but was at a much lower level. Upon intravenous infusion to steady state, FRM-1CCSF and Cu,b were similar, accounting for 61% and 69% of the Cu,p, indicating a case of largely passive diffusion-governed brain penetration where CCSF served as a good surrogate for Cu,b. On the contrary, FRM-2CCSF and Cu,b were remarkably lower than Cu,p (17% and 8% of Cu,p, respectively), suggesting that FRM-2 brain penetration was severely impaired by P-gp-mediated efflux and CCSF underestimated this impact. A semi-physiologically based pharmacokinetic (PBPK) model was constructed that adequately described the temporal profiles of the compounds in the plasma, brain and CSF. Our work provided some insight into the relative importance of blood-brain barrier (BBB) and blood-CSF barrier (BCSFB) in modulating CCSF. PMID:25091561

  14. The Alzheimer’s Association external quality control program for cerebrospinal fluid biomarkers

    PubMed Central

    Mattsson, Niklas; Andreasson, Ulf; Persson, Staffan; Arai, Hiroyuki; Batish, Sat Dev; Bernardini, Sergio; Bocchio-Chiavetto, Luisella; Blankenstein, Marinus A.; Carrillo, Maria C.; Chalbot, Sonia; Coart, Els; Chiasserini, Davide; Cutler, Neal; Dahlfors, Gunilla; Duller, Stefan; Fagan, Anne M.; Forlenza, Orestes; Frisoni, Giovanni B.; Galasko, Douglas; Galimberti, Daniela; Hampel, Harald; Handberg, Aase; Heneka, Michael T.; Herskovits, Adrianna Z.; Herukka, Sanna-Kaisa; Holtzman, David M.; Humpel, Christian; Hyman, Bradley T.; Iqbal, Khalid; Jucker, Mathias; Kaeser, Stephan A.; Kaiser, Elmar; Kapaki, Elisabeth; Kidd, Daniel; Klivenyi, Peter; Knudsen, Cindy S.; Kummer, Markus P.; Lui, James; Lladó, Albert; Lewczuk, Piotr; Li, Qiao-Xin; Martins, Ralph; Masters, Colin; McAuliffe, John; Mercken, Marc; Moghekar, Abhay; Molinuevo, José Luis; Montine, Thomas J.; Nowatzke, William; O’Brien, Richard; Otto, Markus; Paraskevas, George P.; Parnetti, Lucilla; Petersen, Ronald C.; Prvulovic, David; de Reus, Herman P. M.; Rissman, Robert A.; Scarpini, Elio; Stefani, Alessandro; Soininen, Hilkka; Schröder, Johannes; Shaw, Leslie M.; Skinningsrud, Anders; Skrogstad, Brith; Spreer, Annette; Talib, Leda; Teunissen, Charlotte; Trojanowski, John Q.; Tumani, Hayrettin; Umek, Robert M.; Van Broeck, Bianca; Vanderstichele, Hugo; Vecsei, Laszlo; Verbeek, Marcel M.; Windisch, Manfred; Zhang, Jing; Zetterberg, Henrik; Blennow, Kaj

    2013-01-01

    Background The cerebrospinal fluid (CSF) biomarkers amyloid ? (A?)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer’s disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer’s Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program. Methods The program is open for laboratories using commercially available kits for A?, T-tau, or P-tau. CSF samples (aliquots of pooled CSF) are sent for analysis several times a year from the Clinical Neurochemistry Laboratory at the Molndal campus of the University of Gothenburg, Sweden. Each round consists of three quality control samples. Results Forty laboratories participated. Twenty-six used INNOTESTenzyme-linked immunosorbent assay kits, 14 used Luminex xMAP with the INNO-BIA AlzBio3 kit (both measure A?-(1-42), P-tau(181P), and T-tau), and 5 used Meso Scale Discovery with the A? triplex (A?N-42, A?N-40, and A?N-38) or T-tau kits. The total coefficients of variation between the laboratories were 13% to 36%. Five laboratories analyzed the samples six times on different occasions. Within-laboratory precisions differed considerably between biomarkers within individual laboratories. Conclusions Measurements of CSF AD biomarkers show large between-laboratory variability, likely caused by factors related to analytical procedures and the analytical kits. Standardization of laboratory procedures and efforts by kit vendors to increase kit performance might lower variability, and will likely increase the usefulness of CSF AD biomarkers. PMID:21784349

  15. Active removal of inorganic phosphate from cerebrospinal fluid by the choroid plexus.

    PubMed

    Guerreiro, Pedro M; Bataille, Amy M; Parker, Sonda L; Renfro, J Larry

    2014-06-01

    The P(i) concentration of mammalian cerebrospinal fluid (CSF) is about one-half that of plasma, a phenomenon also shown here in the spiny dogfish, Squalus acanthias. The objective of the present study was to characterize the possible role of the choroid plexus (CP) in determining CSF P(i) concentration. The large sheet-like fourth CP of the shark was mounted in Ussing chambers where unidirectional (33)P(i) fluxes revealed potent active transport from CSF to the blood side under short-circuited conditions. The flux ratio was 8:1 with an average transepithelial resistance of 87 ± 17.9 ?·cm(2) and electrical potential difference of +0.9 ± 0.17 mV (CSF side positive). Active P(i) absorption from CSF was inhibited by 10 mM arsenate, 0.2 mM ouabain, Na(+)-free medium, and increasing the K(+) concentration from 5 to 100 mM. Li(+) stimulated transport twofold compared with Na(+)-free medium. Phosphonoformic acid (1 mM) had no effect on active P(i) transport. RT-PCR revealed both P(i) transporter (PiT)1 and PiT2 (SLC20 family) gene expression, but no Na(+)-P(i) cotransporter II (SLC34 family) expression, in the shark CP. PiT2 immunoreactivity was shown by immunoblot analysis and localized by immunohistochemistry in (or near) the CP apical microvillar membranes of both the shark and rat. PiT1 appeared to be localized primarily to vascular endothelial cells. Taken together, these data indicate that the CP actively removes P(i) from CSF. This process has transport properties consistent with a PiT2, Na(+)-dependent transporter that is located in the apical region of the CP epithelium. PMID:24740787

  16. Multiplicity of cerebrospinal fluid functions: New challenges in health and disease

    PubMed Central

    Johanson, Conrad E; Duncan, John A; Klinge, Petra M; Brinker, Thomas; Stopa, Edward G; Silverberg, Gerald D

    2008-01-01

    This review integrates eight aspects of cerebrospinal fluid (CSF) circulatory dynamics: formation rate, pressure, flow, volume, turnover rate, composition, recycling and reabsorption. Novel ways to modulate CSF formation emanate from recent analyses of choroid plexus transcription factors (E2F5), ion transporters (NaHCO3 cotransport), transport enzymes (isoforms of carbonic anhydrase), aquaporin 1 regulation, and plasticity of receptors for fluid-regulating neuropeptides. A greater appreciation of CSF pressure (CSFP) is being generated by fresh insights on peptidergic regulatory servomechanisms, the role of dysfunctional ependyma and circumventricular organs in causing congenital hydrocephalus, and the clinical use of algorithms to delineate CSFP waveforms for diagnostic and prognostic utility. Increasing attention focuses on CSF flow: how it impacts cerebral metabolism and hemodynamics, neural stem cell progression in the subventricular zone, and catabolite/peptide clearance from the CNS. The pathophysiological significance of changes in CSF volume is assessed from the respective viewpoints of hemodynamics (choroid plexus blood flow and pulsatility), hydrodynamics (choroidal hypo- and hypersecretion) and neuroendocrine factors (i.e., coordinated regulation by atrial natriuretic peptide, arginine vasopressin and basic fibroblast growth factor). In aging, normal pressure hydrocephalus and Alzheimer's disease, the expanding CSF space reduces the CSF turnover rate, thus compromising the CSF sink action to clear harmful metabolites (e.g., amyloid) from the CNS. Dwindling CSF dynamics greatly harms the interstitial environment of neurons. Accordingly the altered CSF composition in neurodegenerative diseases and senescence, because of adverse effects on neural processes and cognition, needs more effective clinical management. CSF recycling between subarachnoid space, brain and ventricles promotes interstitial fluid (ISF) convection with both trophic and excretory benefits. Finally, CSF reabsorption via multiple pathways (olfactory and spinal arachnoidal bulk flow) is likely complemented by fluid clearance across capillary walls (aquaporin 4) and arachnoid villi when CSFP and fluid retention are markedly elevated. A model is presented that links CSF and ISF homeostasis to coordinated fluxes of water and solutes at both the blood-CSF and blood-brain transport interfaces. Outline 1 Overview 2 CSF formation 2.1 Transcription factors 2.2 Ion transporters 2.3 Enzymes that modulate transport 2.4 Aquaporins or water channels 2.5 Receptors for neuropeptides 3 CSF pressure 3.1 Servomechanism regulatory hypothesis 3.2 Ontogeny of CSF pressure generation 3.3 Congenital hydrocephalus and periventricular regions 3.4 Brain response to elevated CSF pressure 3.5 Advances in measuring CSF waveforms 4 CSF flow 4.1 CSF flow and brain metabolism 4.2 Flow effects on fetal germinal matrix 4.3 Decreasing CSF flow in aging CNS 4.4 Refinement of non-invasive flow measurements 5 CSF volume 5.1 Hemodynamic factors 5.2 Hydrodynamic factors 5.3 Neuroendocrine factors 6 CSF turnover rate 6.1 Adverse effect of ventriculomegaly 6.2 Attenuated CSF sink action 7 CSF composition 7.1 Kidney-like action of CP-CSF system 7.2 Altered CSF biochemistry in aging and disease 7.3 Importance of clearance transport 7.4 Therapeutic manipulation of composition 8 CSF recycling in relation to ISF dynamics 8.1 CSF exchange with brain interstitium 8.2 Components of ISF movement in brain 8.3 Compromised ISF/CSF dynamics and amyloid retention 9 CSF reabsorption 9.1 Arachnoidal outflow resistance 9.2 Arachnoid villi vs. olfactory drainage routes 9.3 Fluid reabsorption along spinal nerves 9.4 Reabsorption across capillary aquaporin channels 10 Developing translationally effective models for restoring CSF balance 11 Conclusion PMID:18479516

  17. PCR primers and probes for the 16S rRNA gene of most species of pathogenic bacteria, including bacteria found in cerebrospinal fluid.

    PubMed Central

    Greisen, K; Loeffelholz, M; Purohit, A; Leong, D

    1994-01-01

    A set of broad-range PCR primers for the 16S rRNA gene in bacteria were tested, along with three series of oligonucleotide probes to detect the PCR product. The first series of probes is broad in range and consists of a universal bacterial probe, a gram-positive probe, a Bacteroides-Flavobacterium probe, and two probes for other gram-negative species. The second series was designed to detect PCR products from seven major bacterial species or groups frequently causing meningitis: Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae, S. agalactiae, Escherichia coli and other enteric bacteria, Listeria monocytogenes, and Staphylococcus aureus. The third series was designed for the detection of DNA from species or genera commonly considered potential contaminants of clinical samples, including cerebrospinal fluid (CSF): Bacillus, Corynebacterium, Propionibacterium, and coagulase-negative Staphylococcus spp. The primers amplified DNA from all 124 different species of bacteria tested. Southern hybridization testing of the broad-range probes with washes containing 3 M tetramethylammonium chloride indicated that this set of probes correctly identified all but two of the 102 bacterial species tested, the exceptions being Deinococcus radiopugnans and Gardnerella vaginalis. The gram-negative and gram-positive probes hybridized to isolates of two newly characterized bacteria, Alloiococcus otitis and Rochalimaea henselii, as predicted by Gram stain characteristics. The CSF pathogen and contaminant probe sequences were compared with available sequence information and with sequencing data for 32 different species. Testing of the CSF pathogen and contaminant probes against DNA from over 60 different strains indicated that, with the exception of the coagulase-negative Staphylococcus probes, these probes provided the correct identification of bacterial species known to be found in CSF. Images PMID:7512093

  18. Treating Meningitis

    MedlinePLUS

    ... 2012;79;e190-e192 Neurology Steven Karceski Treating meningitis This information is current as of November 26, ... infections http://www.neurology.org//cgi/collection/meningitis Meningitis http://www.neurology.org//cgi/collection/fungal_infections ...

  19. Impact of Cerebrospinal Fluid Shunting for Idiopathic Normal Pressure Hydrocephalus on the Amyloid Cascade

    PubMed Central

    Moriya, Masao; Miyajima, Masakazu; Nakajima, Madoka; Ogino, Ikuko; Arai, Hajime

    2015-01-01

    The aim of this study was to determine whether the improvement of cerebrospinal fluid (CSF) flow dynamics by CSF shunting, can suppress the oligomerization of amyloid ?-peptide (A?), by measuring the levels of Alzheimer’s disease (AD)-related proteins in the CSF before and after lumboperitoneal shunting. Lumbar CSF from 32 patients with idiopathic normal pressure hydrocephalus (iNPH) (samples were obtained before and 1 year after shunting), 15 patients with AD, and 12 normal controls was analyzed for AD-related proteins and APLP1-derived A?-like peptides (APL1?) (a surrogate marker for A?). We found that before shunting, individuals with iNPH had significantly lower levels of soluble amyloid precursor proteins (sAPP) and A?38 compared to patients with AD and normal controls. We divided the patients with iNPH into patients with favorable (improvement ? 1 on the modified Rankin Scale) and unfavorable (no improvement on the modified Rankin Scale) outcomes. Compared to the unfavorable outcome group, the favorable outcome group showed significant increases in A?38, 40, 42, and phosphorylated-tau levels after shunting. In contrast, there were no significant changes in the levels of APL1?25, 27, and 28 after shunting. After shunting, we observed positive correlations between sAPP? and sAPP?, A?38 and 42, and APL1?25 and 28, with shifts from sAPP? to sAPP?, from APL1?28 to 25, and from A?42 to 38 in all patients with iNPH. Our results suggest that A? production remained unchanged by the shunt procedure because the levels of sAPP and APL1? were unchanged. Moreover, the shift of A? from oligomer to monomer due to the shift of A?42 (easy to aggregate) to A?38 (difficult to aggregate), and the improvement of interstitial-fluid flow, could lead to increased A? levels in the CSF. Our findings suggest that the shunting procedure can delay intracerebral deposition of A? in patients with iNPH. PMID:25821958

  20. PCR-based national bacterial meningitis surveillance in Turkey: years 2006 to 2009.

    PubMed

    Toprak, Demet; Soysal, Ahmet; Toruno?lu, Mehmet Ali; Turgut, Mehmet; Türko?lu, Salih; Pimenta, Fabiana Cristina; Carvalho, Maria da Gloria; Wang, Xin; Mayer, Leonard; Altnkanat, Gül?en; Söyletir, Güner; Mete, Birgül; Bakr, Mustafa

    2014-10-01

    Polymerase chain reaction-based surveillance for bacterial meningitis including 841 children revealed 246 with bacterial DNA in cerebrospinal fluid samples of which 53% were Streptococcus pneumoniae, 19% Neisseria meningitidis, and 16% Haemophilus influenzae type b. The most common S. pneumoniae serotypes/serogroups were 1, 19F, 6A/6B, 23F, 5, 14, 18 and 19A. Among 47 meningococci, 86% were serogroup B, 6% serogroup C, 3% serogroup A, 3% serogroup X and 3% serogroup W. PMID:25361189

  1. Aseptic meningitis in children: Correlation between fever and interferon-gamma level

    Microsoft Academic Search

    I. Minamishima; S. Ohga; E. Ishii; C. Miyazaki; K. Hamada; K. Akazawa; K. Ueda

    1991-01-01

    We studied the correlation between interleukin-1 beta (IL-1?), tumour necrosis factor alpha (TNF-?) and interferon gamma (IFN-?) in cerebrospinal fluid (CSF) and clinical\\/laboratory findings in children with aseptic meningitis. In 19\\/27 patients (70%), the CSF IFN level was high at initial diagnosis, and reduced to a low or undetectable level during the convalescent phase (5–14 days later) of the disease.

  2. Leukemic meningitis in a patient with hairy cell leukemia. A case report

    SciTech Connect

    Wolfe, D.W.; Scopelliti, J.A.; Boselli, B.D.

    1984-09-15

    Central nervous system involvement has not previously been described in patients with hairy cell leukemia (HCL). A patient is reported who presented with meningeal involvement as his initial symptom of HCL. Diagnosis was established by morphologic and cytochemical studies of his cerebrospinal fluid (CSF) and bone marrow. Treatment with whole-brain irradiation and intrathecal chemotherapy was successful in clearing leukemic cells from the CSF with resolution of symptoms.

  3. Invader plus method detects herpes simplex virus in cerebrospinal fluid and simultaneously differentiates types 1 and 2.

    PubMed

    Allawi, Hatim T; Li, Haijing; Sander, Tamara; Aslanukov, Azamat; Lyamichev, Victor I; Blackman, Amondrea; Elagin, Slava; Tang, Yi-Wei

    2006-09-01

    We report here on the development and validation of a prototype Invader Plus method for the qualitative detection of herpes simplex virus types 1 and 2 in cerebrospinal fluid (CSF). The method combines PCR and Invader techniques in a single, closed-tube, continuous-reaction format that gives an analytical sensitivity of approximately 10 copies per reaction. The clinical sensitivity and specificity were 100.0% and 98.6%, respectively, when the results of the method were validated against the results obtained with a PCR colorimetric microtiter plate system by use of clinical CSF specimens. PMID:16954297

  4. Cerebrospinal fluid S-adenosylmethionine in depression and dementia: effects of treatment with parenteral and oral S-adenosylmethionine.

    PubMed Central

    Bottiglieri, T; Godfrey, P; Flynn, T; Carney, M W; Toone, B K; Reynolds, E H

    1990-01-01

    Cerebrospinal fluid (CSF) S-adenosylmethionine (SAM) levels were significantly lower in severely depressed patients than in a neurological control group. The administration of SAM either intravenously or orally is associated with a significant rise of CSF SAM, indicating that it crosses the blood-brain barrier in humans. These observations provide a rational basis for the antidepressant effect of SAM, which has been confirmed in several countries. CSF SAM levels were low in a group of patients with Alzheimer's dementia suggesting a possible disturbance of methylation in such patients and the need for trials of SAM treatment. PMID:2292704

  5. Lack of usutu virus RNA in cerebrospinal fluid of patients with encephalitis of unknown etiology, Tuscany, Italy.

    PubMed

    Maggi, Fabrizio; Mazzetti, Paola; Focosi, Daniele; Macera, Lisa; Scagnolari, Carolina; Manzin, Aldo; Antonelli, Guido; Nelli, Luca Ceccherini

    2015-06-01

    Usutu virus (USUV) is an African mosquito-borne flavivirus associated with human neurological disorders in Europe. Recently, USUV introduction in Europe has been traced back to Eurasian blackbirds deaths in the Tuscany region of Italy in 1996. Ninety-six cerebrospinal fluid (CSF) samples from patients with encephalitis of unknown etiology diagnosed in 2010-2013 were screened to determine whether USUV circulates in humans in Tuscany. Using real-time polymerase chain reaction, no positive patient was found. USUV does not seem to cause neuroinvasive disorders in humans in Tuscany. J. Med. Virol. 87:913-916, 2015. © 2015 Wiley Periodicals, Inc. PMID:25712912

  6. Analysis of L-serine-O-phosphate in cerebrospinal spinal fluid by derivatization-liquid chromatography/mass spectrometry.

    PubMed

    McNaney, Colleen A; Benitex, Yulia; Luchetti, David; Labasi, Jeffrey M; Olah, Timothy V; Morgan, Daniel G; Drexler, Dieter M

    2014-05-01

    L-serine-O-phosphate (L-SOP), the precursor of L-serine, is a potent agonist against the group III metabotropic glutamate receptors (mGluRs) and, thus, is of interest as a potential biomarker for monitoring modulation of neurotransmitter release. So far, no reports are available on the analysis of L-SOP in cerebrospinal fluid (CSF). Here a novel method is presented to determine L-SOP levels in CSF employing precolumn derivatization with (5-N-succinimidoxy-5-oxopentyl)triphenylphosphonium bromide (SPTPP) coupled to liquid chromatography/mass spectrometry (derivatization-LC/MS, d-LC/MS). PMID:24534252

  7. Ultrastructure of the cerebrospinal fluid outflow along the optic nerve into the lymphatic system

    Microsoft Academic Search

    Wolf Lüdemann; Dirk Berens von Rautenfeld; Madjid Samii; Thomas Brinker

    2005-01-01

    Object To explain the spontaneous CSF outflow into the orbit, the ultrastructure of the perineural meningeal layers at the distal and the proximal portions of the optic nerve were compared. Methods Ten cats were perfusion fixated and the orbital content removed for transmission and scanning electron microscopy. In five animals a 60-min cisternal infusion of contrast medium at low intracranial

  8. First Case of Human Infection Due to Pseudomonas fulva, an Environmental Bacterium Isolated from Cerebrospinal Fluid ?

    PubMed Central

    Almuzara, Marisa N.; Vazquez, Miryam; Tanaka, Naoto; Turco, Marisa; Ramirez, Maria S.; Lopez, Eduardo L.; Pasteran, Fernando; Rapoport, Melina; Procopio, Adriana; Vay, Carlos A.

    2010-01-01

    We report the first case of human infection due to Pseudomonas fulva. P. fulva caused acute meningitis following the placement of a drainage system in a 2-year-old female. Additionally, the isolate displayed a VIM-2 carbapenemase in a class 1 integron context. PMID:20032258

  9. First case of human infection due to Pseudomonas fulva, an environmental bacterium isolated from cerebrospinal fluid.

    PubMed

    Almuzara, Marisa N; Vazquez, Miryam; Tanaka, Naoto; Turco, Marisa; Ramirez, Maria S; Lopez, Eduardo L; Pasteran, Fernando; Rapoport, Melina; Procopio, Adriana; Vay, Carlos A

    2010-02-01

    We report the first case of human infection due to Pseudomonas fulva. P. fulva caused acute meningitis following the placement of a drainage system in a 2-year-old female. Additionally, the isolate displayed a VIM-2 carbapenemase in a class 1 integron context. PMID:20032258

  10. Human Parasitic Meningitis Caused by Angiostrongylus cantonensis Infection in Taiwan

    PubMed Central

    Chen, Yao-Shen; Yen, Chuan-Min

    2013-01-01

    The major cause of eosinophilic meningitis in Taiwan is Angiostrongylus cantonensis. Humans are infected by ingesting terrestrial and freshwater snails and slugs. In 1998 and 1999, two outbreaks of eosinophilic meningitis caused by A. cantonensis infection were reported among 17 adult male immigrant Thai laborers who had eaten raw golden apple snails (Pomacea canaliculata). Another outbreak associated with consuming a health drink consisting of raw vegetable juice was reported in 2001. These adult cases differed from reports in the 1970s and 1980s, in which most of the cases were in children. With improvements in public health and education of foreign laborers, there have since been only sporadic cases in Taiwan. Review of clinical research indicates inconsistent association of Magnetic Resonance Imaging (MRI) results with clinical features of eosinophilic meningitis. MRI features were nonspecific but there was an association between the presence of high brain MRI signal intensities and severity of peripheral and cerebrospinal fluid (CSF) eosinophilia. Inflammatory markers have been identified in the CSF of patients with eosinophlic meningitis caused by A. cantonensis infection, and vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and the matrix metalloproteinase system may be associated with blood-brain barrier disruption. Eosinophilic meningitis caused by A. cantonensis infection is not a reportable disease in Taiwan. It is important that a public advisory and education program be developed to reduce future accidental infection. PMID:23901378

  11. Appearance of the canine meninges in subtraction magnetic resonance images.

    PubMed

    Lamb, Christopher R; Lam, Richard; Keenihan, Erin K; Frean, Stephen

    2014-01-01

    The canine meninges are not visible as discrete structures in noncontrast magnetic resonance (MR) images, and are incompletely visualized in T1-weighted, postgadolinium images, reportedly appearing as short, thin curvilinear segments with minimal enhancement. Subtraction imaging facilitates detection of enhancement of tissues, hence may increase the conspicuity of meninges. The aim of the present study was to describe qualitatively the appearance of canine meninges in subtraction MR images obtained using a dynamic technique. Images were reviewed of 10 consecutive dogs that had dynamic pre- and postgadolinium T1W imaging of the brain that was interpreted as normal, and had normal cerebrospinal fluid. Image-anatomic correlation was facilitated by dissection and histologic examination of two canine cadavers. Meningeal enhancement was relatively inconspicuous in postgadolinium T1-weighted images, but was clearly visible in subtraction images of all dogs. Enhancement was visible as faint, small-rounded foci compatible with vessels seen end on within the sulci, a series of larger rounded foci compatible with vessels of variable caliber on the dorsal aspect of the cerebral cortex, and a continuous thin zone of moderate enhancement around the brain. Superimposition of color-encoded subtraction images on pregadolinium T1- and T2-weighted images facilitated localization of the origin of enhancement, which appeared to be predominantly dural, with relatively few leptomeningeal structures visible. Dynamic subtraction MR imaging should be considered for inclusion in clinical brain MR protocols because of the possibility that its use may increase sensitivity for lesions affecting the meninges. PMID:24833219

  12. Human parasitic meningitis caused by Angiostrongylus cantonensis infection in Taiwan.

    PubMed

    Tsai, Hung-Chin; Chen, Yao-Shen; Yen, Chuan-Min

    2013-06-01

    The major cause of eosinophilic meningitis in Taiwan is Angiostrongylus cantonensis. Humans are infected by ingesting terrestrial and freshwater snails and slugs. In 1998 and 1999, two outbreaks of eosinophilic meningitis caused by A. cantonensis infection were reported among 17 adult male immigrant Thai laborers who had eaten raw golden apple snails (Pomacea canaliculata). Another outbreak associated with consuming a health drink consisting of raw vegetable juice was reported in 2001. These adult cases differed from reports in the 1970s and 1980s, in which most of the cases were in children. With improvements in public health and education of foreign laborers, there have since been only sporadic cases in Taiwan. Review of clinical research indicates inconsistent association of Magnetic Resonance Imaging (MRI) results with clinical features of eosinophilic meningitis. MRI features were nonspecific but there was an association between the presence of high brain MRI signal intensities and severity of peripheral and cerebrospinal fluid (CSF) eosinophilia. Inflammatory markers have been identified in the CSF of patients with eosinophilic meningitis caused by A. cantonensis infection, and vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and the matrix metalloproteinase system may be associated with blood-brain barrier disruption. Eosinophilic meningitis caused by A. cantonensis infection is not a reportable disease in Taiwan. It is important that a public advisory and education program be developed to reduce future accidental infection. PMID:23901378

  13. Distribution in cerebrospinal fluid, blood, and lymph of epidurally injected morphine and inulin in dogs

    SciTech Connect

    Durant, P.A.; Yaksh, T.L.

    1986-06-01

    We describe procedures for catheterizing the epidural space, the azygos vein, and the thoracic lymph duct of dogs without using fluoroscopy. The success rates of the procedures were 100, 80, and 50%, respectively (n = 10). To assess the validity of the model, /sup 3/H-morphine and unlabeled morphine (2 mg) were injected epidurally in ten dogs. Lumbar cerebrospinal fluid (CSF), azygos venous blood, arterial blood, and lymph were sampled before and 5, 20, 60, 120, 180, 240, 300 and 360 min after injection. During the first 20 min, morphine levels in the azygos vein were about three and ten times greater than arterial and lymphatic levels, respectively (n = 3; P less than 0.01). Morphine levels were significantly greater in the azygos vein (n = 8) and the femoral artery (n = 10) during the first 20 and 60 min than they were later, respectively (P less than 0.05). In the lymph (n = 5), the levels of morphine at 60 min were statistically greater (P less than 0.05) than levels at 4, 5, and 6 hr. At no time were the concurrent arterial and lymph levels different from each other. In the lumbar CSF, the morphine peak concentration was reached 5-60 min after epidural injection and ranged between 5 and 93 micrograms/ml. In the CSF, the levels of morphine were significantly greater during the first 20 min than later (n = 7; P less than 0.05). The washout of the lumbar CSF curve for morphine appeared to be fitted by a two-compartment open model. The t1/2-alpha and t1/2-beta values were 14.7 +/- 7.2 min and 106 +/- 45 min, respectively (mean +/- SD). Cumulative percentages of the epidural dose of morphine passed into the azygos system within the first 5, 20, 60, and 120 min after injection were calculated to be 4.0 +/- 2.1, 23.5 +/- 14.6, 49.2 +/- 34.2, and 55.9 +/- 35.3, respectively (mean +/- SD; n = 8).

  14. Cerebrospinal Fluid (CSF) Neuronal Biomarkers across the Spectrum of HIV Infection: Hierarchy of Injury and Detection

    PubMed Central

    Peterson, Julia; Gisslen, Magnus; Zetterberg, Henrik; Fuchs, Dietmar; Shacklett, Barbara L.; Hagberg, Lars; Yiannoutsos, Constantin T.; Spudich, Serena S.; Price, Richard W.

    2014-01-01

    The character of central nervous system (CNS) HIV infection and its effects on neuronal integrity vary with evolving systemic infection. Using a cross-sectional design and archived samples, we compared concentrations of cerebrospinal fluid (CSF) neuronal biomarkers in 143 samples from 8 HIV-infected subject groups representing a spectrum of untreated systemic HIV progression and viral suppression: primary infection; four groups of chronic HIV infection neuroasymptomatic (NA) subjects defined by blood CD4+ T cells of >350, 200–349, 50–199, and <50 cells/µL; HAD; treatment-induced viral suppression; and ‘elite’ controllers. Samples from 20 HIV-uninfected controls were also examined. The neuronal biomarkers included neurofilament light chain protein (NFL), total and phosphorylated tau (t-tau, p-tau), soluble amyloid precursor proteins alpha and beta (sAPP?, sAPP?) and amyloid beta (A?) fragments 1–42, 1–40 and 1–38. Comparison of the biomarker changes showed a hierarchy of sensitivity in detection and suggested evolving mechanisms with progressive injury. NFL was the most sensitive neuronal biomarker. Its CSF concentration exceeded age-adjusted norms in all HAD patients, 75% of NA CD4<50, 40% of NA CD4 50–199, and 42% of primary infection, indicating common neuronal injury with untreated systemic HIV disease progression as well as transiently during early infection. By contrast, only 75% of HAD subjects had abnormal CSF t-tau levels, and there were no significant differences in t-tau levels among the remaining groups. sAPP? and ? were also abnormal (decreased) in HAD, showed less marked change than NFL with CD4 decline in the absence of HAD, and were not decreased in PHI. The CSF A? peptides and p-tau concentrations did not differ among the groups, distinguishing the HIV CNS injury profile from Alzheimer's disease. These CSF biomarkers can serve as useful tools in selected research and clinical settings for patient classification, pathogenetic analysis, diagnosis and management. PMID:25541953

  15. Cerebrospinal Fluid Biomarker and Brain Biopsy Findings in Idiopathic Normal Pressure Hydrocephalus

    PubMed Central

    Pyykkö, Okko T.; Lumela, Miikka; Rummukainen, Jaana; Nerg, Ossi; Seppälä, Toni T.; Herukka, Sanna-Kaisa; Koivisto, Anne M.; Alafuzoff, Irina; Puli, Lakshman; Savolainen, Sakari; Soininen, Hilkka; Jääskeläinen, Juha E.; Hiltunen, Mikko; Zetterberg, Henrik; Leinonen, Ville

    2014-01-01

    Background The significance of amyloid precursor protein (APP) and neuroinflammation in idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer's disease (AD) is unknown. Objective To investigate the role of soluble APP (sAPP) and amyloid beta (A?) isoforms, proinflammatory cytokines, and biomarkers of neuronal damage in the cerebrospinal fluid (CSF) in relation to brain biopsy A? and hyperphosphorylated tau (HP?) findings. Methods The study population comprised 102 patients with possible NPH with cortical brain biopsies, ventricular and lumbar CSF samples, and DNA available. The final clinical diagnoses were: 53 iNPH (91% shunt-responders), 26 AD (10 mixed iNPH+AD), and 23 others. Biopsy samples were immunostained against A? and HP?. CSF levels of AD-related biomarkers (A?42, p-tau, total tau), non-AD-related A? isoforms (A?38, A?40), sAPP isoforms (sAPP?, sAPP?), proinflammatory cytokines (several interleukins (IL), interferon-gamma, monocyte chemoattractant protein-1, tumor necrosis factor-alpha) and biomarkers of neuronal damage (neurofilament light and myelin basic protein) were measured. All patients were genotyped for APOE. Results Lumbar CSF levels of sAPP? were lower (p<0.05) in patients with shunt-responsive iNPH compared to non-iNPH patients. sAPP? showed a similar trend (p?=?0.06). CSF sAPP isoform levels showed no association to A? or HP? in the brain biopsy. Quantified A? load in the brain biopsy showed a negative correlation with CSF levels of A?42 in ventricular (r?=??0.295, p?=?0.003) and lumbar (r?=??0.356, p?=?0.01) samples, while the levels of A?38 and A?40 showed no correlation. CSF levels of proinflammatory cytokines and biomarkers of neuronal damage did not associate to the brain biopsy findings, diagnosis, or shunt response. Higher lumbar/ventricular CSF IL-8 ratios (p<0.001) were seen in lumbar samples collected after ventriculostomy compared to the samples collected before the procedure. Conclusions The role of sAPP isoforms in iNPH seems to be independent from the amyloid cascade. No neuroinflammatory background was observed in iNPH or AD. PMID:24638077

  16. Identification and Validation of Novel Cerebrospinal Fluid Biomarkers for Staging Early Alzheimer's Disease

    PubMed Central

    Malone, James P.; Shah, Aarti R.; Gilmore, Petra; Davis, Alan E.; Roe, Catherine M.; Peskind, Elaine R.; Li, Ge; Galasko, Douglas R.; Clark, Christopher M.; Quinn, Joseph F.; Kaye, Jeffrey A.; Morris, John C.; Holtzman, David M.; Townsend, R. Reid; Fagan, Anne M.

    2011-01-01

    Background Ideally, disease modifying therapies for Alzheimer disease (AD) will be applied during the ‘preclinical’ stage (pathology present with cognition intact) before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF) proteome. Methods and Findings CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1) (n?=?24) and cognitively normal controls (CDR 0) (n?=?24) were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS) identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA). Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C) distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and A?42 ELISAs) to a larger independent cohort (n?=?292) that included individuals with very mild dementia (CDR 0.5). Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM) and CDR 1 from CDR<1 (tau, chromogranin A, carnosinase I) with areas under the curve of 0.90 (0.85–0.94 95% confidence interval [CI]) and 0.88 (0.81–0.94 CI), respectively. Conclusions Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I) can improve the diagnostic accuracy of A?42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel might improve clinical trial efficiency by guiding subject enrollment and monitoring disease progression. Further studies will be required to validate this panel and evaluate its potential for distinguishing AD from other dementing conditions. PMID:21264269

  17. A diagnostic scale for Alzheimer’s disease based on cerebrospinal fluid biomarker profiles

    PubMed Central

    2014-01-01

    Introduction The relevance of the cerebrospinal fluid (CSF) biomarkers for the diagnosis of Alzheimer’s disease (AD) and related disorders is clearly established. However, the question remains on how to use these data, which are often heterogeneous (not all biomarkers being pathologic). The objective of this study is to propose to physicians in memory clinics a biologic scale of probabilities that the patient with cognitive impairments has an Alzheimer’s disease (AD) pathologic process. Methods For that purpose, we took advantage of the multicenter data of our Paris-North, Lille, and Montpellier (PLM) study, which has emerged through the initial sharing of information from these memory centers. Different models combining the CSF levels of amyloid-? 42, tau, and p-tau(181) were tested to generate categories of patients with very low (<10%), low (<25%), high (>75%), and very high predictive values (>90%) for positive AD. In total, 1,273 patients (646 AD and 627 non-AD) from six independent memory-clinic cohorts were included. Results A prediction model based on logistic regressions achieved a very good stratification of the population but had the disadvantages of needing mathematical optimization and being difficult to use in daily clinical practice. Remarkably, a simple and intuitive model based on the number (from zero to three) of three pathologic CSF biomarkers resulted in a very efficient predictive scale for AD in patients seen in memory clinics. The scale’s overall predictive value for AD for the different categories were as follows: class 0, 9.6% (95% confidence interval (CI), 6.0% to 13.2%); class 1, 24.7% (95% CI, 18.0% to 31.3%); class 2, 77.2% (95% CI, 67.8% to 86.5%); and class 3, 94.2% (95% CI, 90.7% to 97.7%). In addition, with this scale, significantly more patients were correctly classified than with the logistic regression. Its superiority in model performance was validated by the computation of the net reclassification index (NRI). The model was also validated in an independent multicenter dataset of 408 patients (213 AD and 195 non-AD). Conclusions In conclusion, we defined a new scale that could be used to facilitate the interpretation and routine use of multivariate CSF data, as well as helping the stratification of patients in clinical research trials. PMID:25478015

  18. Changes in Oxidative Damage, Inflammation and [NAD(H)] with Age in Cerebrospinal Fluid

    PubMed Central

    Guest, Jade; Grant, Ross; Mori, Trevor A.; Croft, Kevin D.

    2014-01-01

    An extensive body of evidence indicates that oxidative stress and inflammation play a central role in the degenerative changes of systemic tissues in aging. However a comparatively limited amount of data is available to verify whether these processes also contribute to normal aging within the brain. High levels of oxidative damage results in key cellular changes including a reduction in available nicotinamide adenine dinucleotide (NAD+), an essential molecule required for a number of vital cellular processes including DNA repair, immune signaling and epigenetic processing. In this study we quantified changes in [NAD(H)] and markers of inflammation and oxidative damage (F2-isoprostanes, 8-OHdG, total antioxidant capacity) in the cerebrospinal fluid (CSF) of healthy humans across a wide age range (24–91 years). CSF was collected from consenting patients who required a spinal tap for the administration of anesthetic. CSF of participants aged >45 years was found to contain increased levels of lipid peroxidation (F2-isoprostanes) (p?=?0.04) and inflammation (IL-6) (p?=?0.00) and decreased levels of both total antioxidant capacity (p?=?0.00) and NAD(H) (p?=?0.05), compared to their younger counterparts. A positive association was also observed between plasma [NAD(H)] and CSF NAD(H) levels (p?=?0.03). Further analysis of the data identified a relationship between alcohol intake and CSF [NAD(H)] and markers of inflammation. The CSF of participants who consumed >1 standard drink of alcohol per day contained lower levels of NAD(H) compared to those who consumed no alcohol (p<0.05). An increase in CSF IL-6 was observed in participants who reported drinking >0–1 (p<0.05) and >1 (p<0.05) standard alcoholic drinks per day compared to those who did not drink alcohol. Taken together these data suggest a progressive age associated increase in oxidative damage, inflammation and reduced [NAD(H)] in the brain which may be exacerbated by alcohol intake. PMID:24454842

  19. The cerebrospinal fluid proteome in HIV infection: change associated with disease severity.

    SciTech Connect

    Angel, Thomas E.; Jacobs, Jon M.; Spudich, Serena S.; Gritsenko, Marina A.; Fuchs, Dietmar; Liegler, Teri; Zetterberg, Henrik; Camp, David G.; Price, Richard W.; Smith, Richard D.

    2012-03-20

    Central nervous system (CNS) infection is a constant feature of systemic HIV infection with a clinical spectrum that ranges from chronic asymptomatic infection to severe cognitive and motor dysfunction. Analysis of cerebrospinal fluid (CSF) has played an important part in defining the character of this evolving infection and response to treatment. To further characterize CNS HIV infection and its effects, we applied advanced high-throughput proteomic methods to CSF to identify novel proteins and their changes with disease progression and treatment. After establishing an accurate mass and time (AMT) tag database containing 23,141 AMT tags for CSF peptides, we analyzed 91 CSF samples by LC-MS from 12 HIV-uninfected and 14 HIV-infected subjects studied in the context of initiation of antiretroviral and correlated abundances of identified proteins (a) within and between subjects, (b) with all other proteins across the entire sample set, and (c) with 'external' CSF biomarkers of infection (HIV RNA), immune activation (neopterin) and neural injury (neurofilament light chain protein, NFL). We identified a mean of 2,333 +/- 328 (SD) peptides covering 307 +/-16 proteins in the 91 CSF sample set. Protein abundances differed both between and within subjects sampled at different time points and readily separated those with and without HIV infection. Proteins also showed inter-correlations across the sample set that were associated with biologically relevant dynamic processes. One-hundred and fifty proteins showed correlations with the external biomarkers. For example, using a threshold of cross correlation coefficient (Pearson's) {le}0.3 and {ge}0.3 for potentially meaningful relationships, a total of 99 proteins correlated with CSF neopterin (43 negative and 56 positive correlations) and related principally to neuronal plasticity and survival and to innate immunity. Pathway analysis defined several networks connecting the identified proteins, including one with amyloid precursor protein as a central node. Advanced CSF proteomic analysis enabled the identification of an array of novel protein changes across the spectrum of CNS HIV infection and disease. This initial analysis clearly demonstrated the value of contemporary state-of-the-art proteomic CSF analysis as a discovery tool in HIV infection with likely similar application to other neurological inflammatory and degenerative diseases.

  20. Cerebrospinal fluid peptides as potential Parkinson disease biomarkers: a staged pipeline for discovery and validation.

    PubMed

    Shi, Min; Movius, James; Dator, Romel; Aro, Patrick; Zhao, Yanchun; Pan, Catherine; Lin, Xiangmin; Bammler, Theo K; Stewart, Tessandra; Zabetian, Cyrus P; Peskind, Elaine R; Hu, Shu-Ching; Quinn, Joseph F; Galasko, Douglas R; Zhang, Jing

    2015-03-01

    Finding robust biomarkers for Parkinson disease (PD) is currently hampered by inherent technical limitations associated with imaging or antibody-based protein assays. To circumvent the challenges, we adapted a staged pipeline, starting from our previous proteomic profiling followed by high-throughput targeted mass spectrometry (MS), to identify peptides in human cerebrospinal fluid (CSF) for PD diagnosis and disease severity correlation. In this multicenter study consisting of training and validation sets, a total of 178 subjects were randomly selected from a retrospective cohort, matching age and sex between PD patients, healthy controls, and neurological controls with Alzheimer disease (AD). From ?14,000 unique peptides displaying differences between PD and healthy control in proteomic investigations, 126 peptides were selected based on relevance and observability in CSF using bioinformatic analysis and MS screening, and then quantified by highly accurate and sensitive selected reaction monitoring (SRM) in the CSF of 30 PD patients versus 30 healthy controls (training set), followed by diagnostic (receiver operating characteristics) and disease severity correlation analyses. The most promising candidates were further tested in an independent cohort of 40 PD patients, 38 AD patients, and 40 healthy controls (validation set). A panel of five peptides (derived from SPP1, LRP1, CSF1R, EPHA4, and TIMP1) was identified to provide an area under curve (AUC) of 0.873 (sensitivity = 76.7%, specificity = 80.0%) for PD versus healthy controls in the training set. The performance was essentially confirmed in the validation set (AUC = 0.853, sensitivity = 82.5%, specificity = 82.5%). Additionally, this panel could also differentiate the PD and AD groups (AUC = 0.990, sensitivity = 95.0%, specificity = 97.4%). Furthermore, a combination of two peptides belonging to proteins TIMP1 and APLP1 significantly correlated with disease severity as determined by the Unified Parkinson's Disease Rating Scale motor scores in both the training (r = 0.381, p = 0.038)j and the validation (r = 0.339, p = 0.032) sets. The novel panel of CSF peptides, if validated in independent cohorts, could be used to assist in clinical diagnosis of PD and has the potential to help monitoring or predicting disease progression. PMID:25556233

  1. Relationship of cognitive reserve and cerebrospinal fluid biomarkers to the emergence of clinical symptoms in preclinical Alzheimer's disease.

    PubMed

    Soldan, Anja; Pettigrew, Corinne; Li, Shanshan; Wang, Mei-Cheng; Moghekar, Abhay; Selnes, Ola A; Albert, Marilyn; O'Brien, Richard

    2013-12-01

    The levels of ?-amyloid (A?) and phosphorylated tau (p-tau), as measured in cerebrospinal fluid, have been associated with the risk of progressing from normal cognition to onset of clinical symptoms during preclinical Alzheimer's disease. We examined whether cognitive reserve (CR) modifies this association. Cerebrospinal fluid was obtained at baseline from 239 participants (mean age, 57.2 years) who had been followed for up to 17 years with clinical and cognitive assessments (mean follow-up, 8 years). A composite score based on the National Adult Reading Test, vocabulary, and years of education at baseline was used as an index of CR. Cox regression models showed that the increased risk of progressing from normal cognition to symptom onset was associated with lower CR, lower baseline A?, and higher baseline p-tau. There was no interaction between CR and A?, suggesting that the protective effects of higher CR are equivalent across the observed range of amyloid levels. In contrast, both tau and p-tau interacted with CR, indicating that CR was more protective at lower levels of tau and p-tau. PMID:23916061

  2. Low neuropeptide Y in cerebrospinal fluid in bipolar patients is associated with previous and prospective suicide attempts.

    PubMed

    Sandberg, Johan V; Jakobsson, Joel; Pålsson, Erik; Landén, Mikael; Mathé, Aleksander A

    2014-12-01

    The attempted and accomplished suicide rates in patients with bipolar disorder are 40-50% and 15-20%, respectively. No biological markers that help predict suicide been identified. Human and experimental animal data indicate that dysregulation of the neuropeptide Y (NPY) system plays a role in depression, anxiety, and posttraumatic stress disorder (PTSD). The aim of this study was to explore if low cerebrospinal fluid (CSF) NPY is associated with (1) past suicide attempts, (2) future suicide attempts, and (3) trait anxiety. Lumbar puncture was performed on 120 clinically stable patients with bipolar disorder enrolled in the St Göran Bipolar Project, where the number of previous suicide attempts was documented. NPY-like immunoreactivity (NPY-LI) was determined in cerebrospinal fluid (CSF). Patients were reexamined one year after the lumbar puncture and suicide attempts were recorded. NPY-LI was significantly lower in patients with a history of suicide attempt than in patients who had not attempted suicide prior to lumbar puncture. Importantly, NPY-LI was markedly lower in patients who made a suicide attempt during the follow-up period compared to patients who did not. Patients who attempted suicide during the follow-up also had markedly lower NPY-LI than those with previous suicide attempts who did not reattempt. Our results suggest that low CSF NPY-LI predicts future suicide attempts. The data are in line with the hypothesis that NPY signaling is altered in affective disorders and states of emotional dysregulation. PMID:25453484

  3. Increase in oxidative stress as measured by cerebrospinal fluid lipid peroxidation during treatment for childhood acute lymphoblastic leukemia.

    PubMed

    Ki Moore, Ida M; Gundy, Patricia; Pasvogel, Alice; Montgomery, David W; Taylor, Olga A; Koerner, Kari M; McCarthy, Kathy; Hockenberry, Marilyn J

    2015-03-01

    Five-year survival from childhood acute lymphoblastic leukemia (ALL) approaches 90%, but 40% of survivors experience central nervous system (CNS) treatment-related cognitive problems. Despite considerable evidence for cognitive problems, less is known about mechanisms of neurological injury. Our purpose was to investigate oxidative stress, measured by lipid peroxidation, as a mechanism of CNS treatment-related neurological injury. The sample included 55 children (mean age at diagnosis=6.84 y, SD=3.40) who received intrathecal and intravenous chemotherapy for CNS-directed treatment according to Children's Oncology Group protocols. Glycerophospholipids were extracted from cerebrospinal fluid samples obtained at diagnosis and during intrathecal chemotherapy administration. Unoxidized and oxidized phosphatidylcholine (PC) and phosphatidylinositol (PI) were measured by normal phase high-performance liquid chromatography with diode array detection, and analyzed with a general linear model for repeated measures analysis of variance. Compared with the diagnostic cerebrospinal fluid sample, unoxidized and oxidized PC and PI increased significantly across treatment phases. Amount of intravenous methotrexate received was significantly correlated with oxidized PI, and age at time of ALL diagnosis was significantly associated with oxidized PC. These findings support our hypothesis that oxidative stress is a mechanism of neurological injury associated with CNS-directed treatment for ALL. PMID:25222054

  4. Qualitative evaluation of selective tests for detection of Neospora hughesi antibodies in serum and cerebrospinal fluid of experimentally infected horses.

    PubMed

    Packham, Andrea E; Conrad, Patricia A; Wilson, W David; Jeanes, Lisa V; Sverlow, Karen W; Gardner, Ian A; Daft, Barbara M; Marsh, Antoinette E; Blagburn, Byron L; Ferraro, Gregory L; Barr, Bradd C

    2002-12-01

    Neospora hughesi is a newly recognized protozoan pathogen in horses that causes a myeloencephalitis similar to Sarcocystis neurona. There are no validated serologic tests using the gold standard sera that are currently available to detect specific N. hughesi antibodies and, thus, no tests available to detect antemortem exposure or estimate seroprevalence in the horse. The objectives of the present study were to establish a bank of gold standard equine sera through experimental infections with N. hughesi and to assess several serologic tests for the detection of related protozoan antibodies. Seven horses were inoculated with N. hughesi tachyzoites, and 7 horses received uninfected cell culture material. The horses were monitored, and blood and cerebrospinal fluid were collected repeatedly over a 4-mo period. With the sera, 4 different serologic techniques were evaluated. including a whole-parasite lysate enzyme-linked immunosorbent assay (ELISA), a recombinant protein ELISA, a modified direct agglutination test, and an indirect fluorescent antibody test. Qualitative and quantitative evaluation of the results showed that the N. hughesi indirect fluorescent antibody test (IFAT) consistently discriminated between experimentally infected and noninfected horses, using a cutoff of 1:640. Sera from 3 naturally infected horses had titers >1:640. Cerebrospinal fluid in all but I infected horse had very low N. hughesi IFAT titers (<1:160), starting at postinoculation day 30. PMID:12537119

  5. Detection of herpes simplex virus DNA from cerebrospinal fluid by PCR and a rapid, nonradioactive hybridization technique.

    PubMed

    Kessler, H H; Pierer, K; Weber, B; Sakrauski, A; Santner, B; Stuenzner, D; Gergely, E; Marth, E

    1994-08-01

    A molecular assay for the detection of herpes simplex virus (HSV), including a novel, nonradioactive hybridization technique, was evaluated with a total of 123 cerebrospinal fluid specimens. After DNA extraction, specific HSV DNA sequences were amplified with digoxigenin-labeled primers derived from the DNA polymerase gene-coding region from HSV. Amplified products were detected by the Enzymun-Test DNA detection assay (Boehringer, Mannheim, Federal Republic of Germany), which uses biotinylated probes. Amplification with nonlabeled primers and then Southern blotting and nonradioactive detection of hybrids by the digoxigenin technique was the reference system. The sensitivities of the molecular assays were determined with 10-fold dilutions of plasmid pS4 with the SalI restriction fragment of the DNA polymerase gene obtained from the HSV type 1 strain Angelotti. The Enzymun assay was able to detect all of the 16 positive samples, giving 100% agreement with the Southern blot hybridization results. Optical density values were widely separated for the positive and negative groups of specimens. Ten copies of plasmid pS4 per microliter could be distinctly detected by the Enzymun assay. The cutoff was determined for the hybridization assay, and an equivocal zone was defined. The whole molecular assay including the Enzymun-Test DNA detection proved to be sensitive and easy to use. It may contribute to the rapid and safe detection of HSV DNA in cerebrospinal fluid. PMID:7989536

  6. Atypical Dengue Meningitis in Makkah, Saudi Arabia with Slow Resolving, Prominent Migraine like Headache, Phobia, and Arrhythmia

    PubMed Central

    Mamdouh, Kalakatawi H; Mroog, Kalakatawi M; Hani, Nasser H; Nabil, Elrefae M

    2013-01-01

    Although dengue meningitis is a rare presentation of dengue infection, our aim is to focus on atypical presentation of dengue meningitis that may appear in dengue endemic area like the Makkah region. We report two cases of clinical meningitis with positive dengue virus (DENV) IgM in cerebrospinal fluid, followed for minimal 3 months for their prominent attacks of migraine like headache, phobia, and arrhythmia. With special consideration to attack time, type, severity, and respond to classical therapy, using regular ECG monitoring, visual analog pain score and neuropsychological assessments were done. Both cases showed resistant migraine like headaches to classic anti-migraine therapy except for strong NSAID and narcotics with tendency to have severe to extreme severe daily migraine like headache on early to late afternoon time, associated with non-fatal arrhythmias and extreme death phobia, that resolve slowly in a minimal 3 month period. In conclusion, dengue meningitis in the endemic area may present atypically. PMID:24672183

  7. Human meningitis caused by Streptococcus suis.

    PubMed

    Zalas-Wiecek, Patrycja; Michalska, Anna; Grabczewska, Edyta; Olczak, Anita; Pawlowska, Malgorzata; Gospodarek, Eugenia

    2013-03-01

    Streptococcus suis is an important swine pathogen worldwide, which can be transmitted to human beings by direct contact; therefore, S. suis infections occur mainly in people who handle pigs or pork. We present a case of a patient with S. suis meningitis who worked as a butcher in a meat processing plant for 5 years. The 35-year-old man was admitted to the Department of Infectious Diseases in T. Browicz Memorial Central Infectious Disease and Observation Hospital in Bydgoszcz, Poland, with suspected bacterial meningitis. According to his medical history, the patient had been injured during the processing of pork. A microbiological examination of the cerebrospinal fluid and blood revealed S. suis as a single aetiological factor of this infection. The patient was empirically administered cefotaxime (2.0 g at 8-h intervals) and penicillin (9 million U at 8-h intervals). The patient made a complete recovery and his inflammatory markers normalized. Only the hearing deficit of his right ear did not disappear. An otolaryngologist recommended a 4-week steroid therapy. The patient was not examined because he did not report to the clinic. To our knowledge this is the first described case of human meningitis caused by S. suis in Poland. PMID:23222864

  8. Salmonella berta meningitis in a term neonate.

    PubMed

    Bowe, A C; Fischer, M; Waggoner-Fountain, L A; Heinan, K C; Goodkin, H P; Zanelli, S A

    2014-10-01

    We report the case of a 37-week male infant born via spontaneous vaginal delivery who developed Salmonella berta sepsis and meningitis. The infant was born to a mother with active diarrhea and stool cultures growing S. berta. On day 3, the infant developed poor feeding, lethargy, apnea and bradycardia prompting a sepsis evaluation. Blood, stool and cerebrospinal fluid cultures were positive for S. berta. An electroencephalogram performed for posturing revealed neonatal status epilepticus. Extensive bilateral periventricular venous hemorrhagic infarctions with multiple herniations were seen on brain magnetic resonance imaging. The infant's condition continued to deteriorate despite maximal support and care was redirected towards comfort measures. PMID:25263727

  9. Observations on the transmission, immunology, clinical signs and chemotherapy of dourine (Trypanosoma equiperdum infection) in horses, with special reference to cerebro-spinal fluid.

    PubMed

    Barrowman, P R

    1976-06-01

    This paper is a record of observations on the transmission and clinical signs of dourine in naturally infected cases of known duration, and of temporal and quantitative aspects of the immune response in blood and cerebro-spinal fluid. Included in the record are observations on the presence of Trypanosoma equiperdum parasites in these body fluids and methods for their detection. There is evidence that the occurrence of nervous symptoms and lesions in infected horses is associated with the presence of Trypanosoma equiperdum parasites in cerebro-spinal fluid. The suitability of cerebro-spinal fluid as an environment for the parasite and its relationship with nervous manifestations of the disease are discussed. Observations support the previously reported lesions of peripheral polyneuritis and suggest a possible correltation between the consitstent position of the nervous lesions and the drainage of cerebro-spinal fluid containing the parasite. Chemotherapy with an experimental drug MSbE was used with varying results in 4 horses at different stages of infection. PMID:1018890

  10. Childhood Psychosis and Monoamine Metabolites in Spinal Fluid.

    ERIC Educational Resources Information Center

    Gillberg, Christopher; And Others

    1983-01-01

    Analysis of cerebrospinal fluid of 22 psychotic children, 22 normal controls, and Ss with mental retardation, progressive encephalopathy, or meningitis revealed that psychotic Ss had raised levels of homovanillic acid. Thirteen Ss diagnosed as autistic showed isolated inrease of this metabolite. Increased concentration of mongamines was not…

  11. Noncommunicating Spinal Extradural Meningeal Cyst in Thoracolumbar Spine

    PubMed Central

    Kim, Il Sup; Son, Byung Chul; Lee, Sang Won

    2010-01-01

    Spinal extradural meningeal cyst has been rarely reported, whose etiologies are assumed to be the communication of cerebrospinal fluid (CSF) between intradural subarchnoid space and cyst due to the congenital defect in dura mater. Although the CSF communication due to this defect can be found, in most case, few cases in which there is a lack of the communication have also been reported. We report a case of the huge extradural meningeal cyst occurring in the thoracolumbar spine (from T10 to L2) where there was a lack of the communication between the intradural subarachnoid space and cyst in a 46-year-old man who presented with symptoms that were indicative of progressive paraparesis and leg pain. The patient underwent laminectomy and cyst excision. On intraoperative findings, the dura was intact and there was a lack of the communication with intradural subarachnoid space. Immediately after the surgery, weakness and leg pain disappeared shortly. PMID:21430982

  12. Open-label study to evaluate the pharmacodynamics, clinical efficacy, and safety of meropenem for adult bacterial meningitis in Japan.

    PubMed

    Morita, Akihiko; Kamei, Satoshi; Minami, Masayuki; Yoshida, Kazuto; Kawabata, Satoshi; Kuroda, Hiroshi; Suzuki, Yasushi; Araki, Nobuo; Iwasaki, Yasuo; Kobayashi, Rei; Hayashi, Naoki; Hirayama, Tetsuyuki; Ochiai, Jun; Ueda, Miki; Yamagishi, Yuka; Niwa, Jun-ichi; Shindo, Katsuro; Fukushima, Yoshihisa; Takita, Tomohiro; Sato, Takayuki; Sato, Shigeru; Mikamo, Hiroshige; Iwata, Satoshi

    2014-09-01

    The aim of this study was to assess the efficacy, safety, and concentration of meropenem in cerebrospinal fluid when meropenem (2 g every 8 h) was administered to Japanese adult patients with bacterial meningitis. Five Japanese patients (mean age 60.6 years [range 35-71]) were enrolled. Infection with Streptococcus pneumoniae (three patients), Streptococcus salivarius (one patient), and Staphylococcus aureus (one patient) was confirmed by cerebrospinal fluid culture. Meropenem (2 g every 8 h) was administered to all five patients. Treatment duration ranged from 14 to 28 days (mean 22.6 days). All the patients were successfully treated. The concentration of meropenem in cerebrospinal fluid ranged from 0.27 to 6.40 ?g/ml up to 8.47 h and was over 1 ?g/ml 3 h after starting meropenem infusion. In each patient, the present study confirmed for the first time that the concentration of meropenem in cerebrospinal fluid exceeded the minimal inhibitory concentration for these pathogens. Eleven clinical and laboratory adverse events considered to be related to meropenem were observed in all patients, but no serious adverse event and no discontinuance of treatment due to adverse events occurred. Thus meropenem appeared to be a well-tolerated and effective agent for Japanese adult patients with bacterial meningitis. 2 g every 8 h of meropenem was delivered to CSF and its concentration was exceed in MICs for the detected pathogens. PMID:24882451

  13. The role of an Ommaya reservoir in the management of children with cryptococcal meningitis.

    PubMed

    Jiang, Pei-Fang; Yu, Hui-Min; Zhou, Bo-Lin; Gao, Feng; Shen, Si-Xiang; Xia, Zhe-Zhi; Shui, Quan-Xiang

    2010-02-01

    Cryptococcal meningitis is the most common life-threatening fungal infection and is associated with high mortality in children. Amphotericin B plus flucytosine and fluconazole is the optimal current therapy. Implantation of an Ommaya reservoir for intraventricular infusion of medication and aspiration of cerebrospinal fluid (CSF) for the treatment of increased intracranial pressure (ICP) has been reported. Intraventricular injection of amphotericin B through an Ommaya reservoir in children with cryptococcal meningitis has not been reported previously. We report two children who had cryptococcal meningitis and associated increased intracranial pressure, and were treated with an Ommaya reservoir. Both patients experienced rapid reversal of symptoms. At the time of discharge both patients had recovered and have remained asymptomatic. PMID:19910108

  14. Detection of Toxoplasma gondii in cerebrospinal fluid from AIDS patients by nested PCR and rapid identification of type I allele at B1 gene by RFLP analysis

    Microsoft Academic Search

    Yenisey Alfonso; Jorge Fraga; Narciso Jiménez; Carlos Fonseca; Alberto J. Dorta-Contreras; Raymundo Cox; Virginia Capó; Francisco Bandera; Olga Pomier; Dora Ginorio

    2009-01-01

    Highly active antiretroviral therapy (HAART) has decreased the incidence of opportunistic infections in the central nervous system (CNS) in AIDS patients. However, toxoplasmic encephalitis (TE) still represents the most common cerebral mass lesion in patients infected with human immunodeficiency virus (HIV). The aim of this study was to evaluate nested PCR-B1 using cerebrospinal fluid (CSF) to detect Toxoplasma gondii DNA

  15. Cerebrospinal fluid outflow resistance measurements in the selection of patients for shunt surgery in the normal pressure hydrocephalus syndrome. A controlled trial

    Microsoft Academic Search

    M. Kosteljanetz; A.-M. Nehen; J. Kaalund

    1990-01-01

    Summary In an attempt to determine to what extent the measurement of cerebrospinal fluid (CSF) outflow resistance (Rout) can distinguish patients with normal-pressure hydrocephalus (NPH) who respond to shunt surgery from patients who fail to do so, the authors undertook a controlled trial. Eighteen patients with the diagnosis of NPH entered the study. In connection with the shunt operation all

  16. Chronic changes in cerebrospinal fluid pathways produced by subarachnoid kaolin injection and experimental spinal cord trauma in the rabbit: their relationship with the development of spinal deformity

    Microsoft Academic Search

    Mehmet Turgut; Emre Çullu; Ay?egül Uysal; Mine Ertem Yurtseven; Bülent Alparslan

    2005-01-01

    Post-traumatic cystic changes in cerebrospinal fluid (CSF) pathways such as ventriculomegaly and\\/or hydrosyringomyelia are not uncommon, but their characteristics have not yet been fully clarified. This study was designed to investigate the alterations affecting the CSF pathways in rabbits at a late stage, and to clarify the relationship between these changes and the development of spinal deformity. In this study,

  17. New method for the extraction of viral RNA and DNA from cerebrospinal fluid for use in the polymerase chain reaction assay

    Microsoft Academic Search

    I. Casas; L. Powell; P. E. Klapper; G. M. Cleator

    1995-01-01

    A new, rapid, and simple method for the isolation of either RNA or DNA from cerebrospinal fluid samples for subsequent amplification by specific polymerase chain reaction (PCR) assays is described. The technique involves a single extraction with a guanidinium thiocyanate acid (GuSCN) buffer, and does not require the use of organic solvents. Applied to the recovery of enteroviral RNA, herpes

  18. Increases in bcl-2 protein in cerebrospinal fluid and evidence for programmed cell death in infants and children after severe traumatic brain injury

    Microsoft Academic Search

    Robert S. B. Clark; Patrick M. Kochanek; P. David Adelson; Michael J. Bell; Joseph A. Carcillo; Minzhi Chen; Stephen R. Wisniewski; Keri Janesko; Michael J. Whalen; Steven H. Graham

    2000-01-01

    Objectives: To determine whether bcl-2, a protein that inhibits apoptosis, would be increased in cerebrospinal fluid (CSF) in infants and children after traumatic brain injury (TBI) and to examine the association of bcl-2 concentration with clinical variables. Study design: Bcl-2 was measured in CSF from 23 children (aged 2 months-16 years) with severe TBI and from 19 children without TBI

  19. Value of a single-shot turbo spin-echo pulse sequence for assessing the architecture of the subarachnoid space and the constitutive nature of cerebrospinal fluid.

    PubMed

    Pease, Anthony; Sullivan, Stacey; Olby, Natasha; Galano, Heather; Cerda-Gonzalez, Sophia; Robertson, Ian D; Gavin, Patrick; Thrall, Donald

    2006-01-01

    Three case history reports are presented to illustrate the value of the single-shot turbo spin-echo pulse sequence for assessment of the subarachnoid space. The use of the single-shot turbo spin-echo pulse sequence, which is a heavily T2-weighted sequence, allows for a rapid, noninvasive evaluation of the subarachnoid space by using the high signal from cerebrospinal fluid. This sequence can be completed in seconds rather than the several minutes required for a T2-fast spin-echo sequence. Unlike the standard T2-fast spin-echo sequence, a single-shot turbo spin-echo pulse sequence also provides qualitative information about the protein and the cellular content of the cerebrospinal fluid, such as in patients with inflammatory debris or hemorrhage in the cerebrospinal fluid. Although the resolution of the single-shot turbo spin-echo pulse sequence images is relatively poor compared with more conventional sequences, the qualitative information about the subarachnoid space and cerebrospinal fluid and the rapid acquisition time, make it a useful sequence to include in standard protocols of spinal magnetic resonance imaging. PMID:16700175

  20. Concentration of calcium and magnesium and trace elements (zinc, copper, iron and manganese) in cerebrospinal fluid: A try of a pathophysiological classification

    Microsoft Academic Search

    Elena María González Romarís; Isabel Idoate Cervantes; José Manuel González López; Jesús Fernando Escanero Marcén

    2011-01-01

    The aim of this study is to analyze the variation of the elements (Ca, Mg, Cu, Fe, Zn and Mn) in normal and pathological CSF and develop a classification basing on the increases in cells and proteins and taking into account these variations.A total of 173 cerebrospinal fluids were analyzed. Of these, 37 fulfilled the criteria of normality and, after

  1. Detection of Treponema pallidum subsp. pallidum from Skin Lesions, Serum, and Cerebrospinal Fluid in an Infant with Congenital Syphilis after Clindamycin Treatment of the Mother during Pregnancy?

    PubMed Central

    Woznicová, Vladana; Šmajs, David; Wechsler, Dan; Mat?jková, Petra; Flasarová, Magdalena

    2007-01-01

    We report here a case of congenital syphilis in a newborn after clindamycin treatment in pregnancy. Using PCR detection of tmpC (TP0319) and DNA sequencing of the genes TP0136 and TP0548, DNA sequences identical to Treponema pallidum subsp. pallidum strain SS14 were detected in the infant's skin lesions, serum, and cerebrospinal fluid. PMID:17151205

  2. Alpha and Gamma-Synuclein Proteins Are Present in Cerebrospinal Fluid and Are Increased in Aged Subjects with Neurodegenerative and Vascular Changes

    Microsoft Academic Search

    E. B. Mukaetova-Ladinska; J. Milne; A. Andras; Z. Abdel-All; J. Cerejeira; E. Greally; J. Robson; E. Jaros; R. Perry; I. G. McKeith; C. Brayne; J. Xuereb; A. Cleghorn; J. Doherty; G. McIntosh; I. Milton

    2008-01-01

    Background: Disease-specific biomarkers should reflect a fundamental feature of neuropathology and be validated in neuropathologically confirmed cases. Several synaptic proteins have been described in cerebrospinal fluid (CSF) of patients with dementia. In Lewy body disease ?-synuclein is incorporated within Lewy bodies and ?-, ?- and ?-synucleins in dystrophic neuritis. These pathological changes are expected to be seen in CSF. Methods:

  3. Near-Infrared Light Propagation in an Adult Head Model. I. Modeling of Low-Level Scattering in the Cerebrospinal Fluid Layer

    Microsoft Academic Search

    Eiji Okada; David T. Delpy

    2003-01-01

    Adequate modeling of light propagation in a human head is important for quantitative near-infrared spectroscopy and optical imaging. The presence of a nonscattering cerebrospinal fluid (CSF) that surrounds the brain has been previously shown to have a strong effect on light propagation in the head. However, in reality, a small amount of scattering is caused by the arachnoid trabeculae in

  4. Meningitis - pneumococcal

    MedlinePLUS

    Pneumococcal meningitis is caused by the bacteria Streptococcus pneumoniae (also called pneumococcus). The bacteria is the most common cause of bacterial meningitis in adult. It is the second most common cause ...

  5. High-performance liquid chromatographic determination of metoprolol and alpha-hydroxymetoprolol concentrations in human serum, urine, and cerebrospinal fluid.

    PubMed

    Gengo, F M; Ziemniak, M A; Kinkel, W R; McHugh, W B

    1984-07-01

    A sensitive and simplified high-performance liquid chromatographic procedure was developed for the simultaneous quantification of metoprolol and alpha-hydroxymetoprolol in human serum, as well as cerebrospinal fluid and urine. Following protein precipitation with trichloroacetic acid, the sample was alkalinized with 1 M NaOH and extracted with dichloromethane. The mobile phase consisted of acetonitrile-water (50:50) containing 0.005 M 1-heptanesulfonic acid in 0.001% acetic acid. Using pronetalol as an internal standard, compounds were quantitated using fluorescence detection at 230 nm with a 300-nm emission filter and 0.02 AUFS. Extraction recovery is approximately 80% for both compounds. The lower limits of detection are 5 ng/mL and 4 ng/mL for metoprolol and alpha-hydroxymetoprolol, respectively. PMID:6470961

  6. Changes in Protein Level in the Cerebrospinal Fluid of a Patient with Cerebral Radiation Necrosis Treated with Bevacizumab

    PubMed Central

    Yano, Hirohito; Nakayama, Noriyuki; Morimitsu, Kasumi; Futamura, Manabu; Ohe, Naoyuki; Miwa, Kazuhiro; Shinoda, Jun; Iwama, Toru

    2014-01-01

    A 32-year-old woman underwent surgeries and radiation therapy for astrocytoma. She developed symptomatic radiation necrosis in the lesion, which caused hydrocephalus. She initially underwent ventricular drainage, because the protein level in the cerebrospinal fluid (CSF) was 787 mg/dL, which was too high for shunt surgery. Because she also had breast cancer, which was pathologically diagnosed as an invasive ductal carcinoma, standard bevacizumab therapy in combination with paclitaxel every 2 weeks was selected. Interestingly, after 2 days, the agents had dramatically reduced the CSF protein level. However, it returned to approximately the initial level within 2 weeks. After two courses of this regimen, a ventriculoperitoneal shunt was placed. After 10 courses of this regimen, the CSF protein level decreased to 338 mg/dL, which is less than half of the initial level. Long-term administration of bevacizumab might decrease leakage of protein from the vessels around the ventriculus. PMID:25574147

  7. Stability of JC virus DNA in cerebrospinal fluid specimens preserved with guanidine lysis buffer for quantitative PCR testing.

    PubMed

    Nakamichi, Kazuo; Lim, Chang-Kweng; Saijo, Masayuki

    2014-01-01

    Quantitative PCR testing for JC virus (JCV) DNA in the cerebrospinal fluid (CSF) is one of the diagnostic standards for progressive multifocal leukoencephalopathy (PML). The present study was conducted to examine its reliability using CSF specimens that had been preserved with guanidine lysis buffers in commercial nucleic acid extraction kits under different conditions. When CSFs were mixed with guanidine buffers, JCV DNA levels were not statistically reduced even after storage for 1 month at room temperature or for 3 months at -80?, compared with the control samples. In addition, the JCV DNA level was not decreased in a mixture of CSF and guanidine thiocyanate buffer incubated for 3 days at 56?. These data suggest that CSF specimens mixed with commercial guanidine buffers can be stored without refrigeration, more safely handled, and directly subjected to JCV DNA testing for PML. PMID:25056080

  8. Serum and cerebrospinal fluid antibodies against myelin basic protein and their IgG subclass distribution in multiple sclerosis.

    PubMed Central

    García-Merino, A; Persson, M A; Ernerudh, J; Díaz-Gil, J J; Olsson, T

    1986-01-01

    IgG class antibodies reactive with myelin basic protein (MBP) were determined by enzyme-linked immunosorbent assay (ELISA) in serum and cerebrospinal fluid (CSF) of 37 patients with multiple sclerosis and a control group of 32 patients with tension headache or psychoneurosis. Using standardised amounts of IgG from CSF and serum in ELISA, significantly higher mean antibody levels were found in CSF as well as in serum from the patients with multiple sclerosis. Ten (27%) of the multiple sclerosis CSF samples and 15 (41%) of the multiple sclerosis sera revealed anti MBP antibody levels exceeding 2 SD of the control group. Seven patients (19%) showed exclusive or higher levels of anti MBP antibodies in CSF, suggesting synthesis within the central nervous system. Analysis by ELISA for IgG subclasses of anti MBP antibodies revealed that they were restricted to IgG 1 in four patients and IgG 3 in one. PMID:2428940

  9. The somnogenic T lymphocyte suppressor prostaglandin D2 is selectively elevated in cerebrospinal fluid of advanced sleeping sickness patients.

    PubMed

    Pentreath, V W; Rees, K; Owolabi, O A; Philip, K A; Doua, F

    1990-01-01

    To help to elucidate the changes induced by Trypanosoma brucei gambiense in the central nervous system (CNS) in advanced sleeping sickness patients, levels of interleukin-1 (IL-1) and prostaglandins D2 (PGD2) and E2 (PGE2) were measured by radioimmunoassay in the cerebrospinal fluid (CSF) from 24 patients diagnosed on the criteria of CSF protein, leucocyte count and parasite presence as having CNS (i.e. late stage) involvement, and from 12 patients without CNS involvement. PGD2 concentrations were selectively and markedly elevated in the late stage patients. The increased PGD2 may in part account for the increased somnolence and the immunosuppression within the CNS. Measurement of PGD2 levels in CSF may be a useful criterion for CNS involvement. PMID:2096510

  10. [Case of Charcot-Marie-Tooth disease type 1A with increased cerebrospinal fluid proteins and nerve root hypertrophy].

    PubMed

    Ishigami, Noriko; Kondo, Masaki; Nakagawa, Masanori

    2008-06-01

    We report herein a 54-year-old man who first noticed muscle weakness of the hands and legs and hypesthesia of the legs at 20-years-old. Symptoms gradually worsened. Charcot-Marie-Tooth disease type 1A (CMT 1A) was diagnosed on the basis of a nerve conduction study and PMP22 gene duplication. Increased levels of cerebrospinal fluid proteins were identified and cervical and lumbosacral nerve root hypertrophy was evident on magnetic resonance imaging (MRI). CMT 1A with increased CSF proteins and nerve root hypertrophy was carefully evaluated clinically and electrophysiologically to rule out other motor sensory neuropathies such as CIDP. Increased levels of CSF proteins in this case might have resulted from circulatory disturbance of CSF in hypertrophic nerve roots. PMID:18616154

  11. Clonally expanded plasma cells in the cerebrospinal fluid of patients with central nervous system autoimmune demyelination produce "oligoclonal bands".

    PubMed

    von Büdingen, Hans-Christian; Gulati, Monica; Kuenzle, Sandra; Fischer, Katja; Rupprecht, Tobias A; Goebels, Norbert

    2010-01-25

    Clonally expanded plasma cells (cePC) and oligoclonal IgG (oligoclonal bands, OCB) in the cerebrospinal fluid (CSF) suggest an involvement of B cell mechanisms in autoimmune CNS demyelination. Due to their CSF-restricted occurrence, OCB are commonly believed to be the products of B cells inside the borders of the blood brain barrier. A comparison of CSF cell Ig transcriptomes and CSF-Ig proteomes recently demonstrated, that in multiple sclerosis patients CSF cells are the origin of CSF immunoglobulins. We expand these findings by applying anti-idiotypic antibodies to detect specific heavy chain CDR3 idiotopes of cePC-produced antibodies amongst OCB in the CSF of a patient each with MS and acute disseminated encephalomyelitis. PMID:19900722

  12. Cyto-morphological features of extramedullary acute megakaryoblastic leukemia on fine needle aspiration and cerebrospinal fluid cytology: A case report

    PubMed Central

    Chitragar, Sanjeev; Agarwal, Shipra; Iyer, Venkateswaran K.; Mathur, Sandeep R.; Karak, Asis K.; Chharchhodawala, Taher; Sharma, Atul; Bakhshi, Sameer

    2011-01-01

    Extramedullary deposits may be the presenting feature of acute myeloid leukemia. An early and accurate diagnosis on cytology will aid in correct patient management. This is especially true for patients with acute megakaryoblastic leukemia (AML M7), where bone marrow aspiration may yield only a dry tap. While cytomorphological features of myeloid sarcoma of other types are well recognized due to its rarity, there are only two case reports discussing the morphological details of megakaryoblastic differentiation on aspiration cytology. We present the case of a 25-year-old patient with extramedullary involvement of lymph node and cerebrospinal fluid by AML M7, describing in detail, the morphological features on aspiration as well as exfoliative cytology. PMID:22022337

  13. Streptococcus pneumoniae Serotype-2 Childhood Meningitis in Bangladesh: A Newly Recognized Pneumococcal Infection Threat

    PubMed Central

    Saha, Samir K.; Al Emran, Hassan M.; Hossain, Belal; Darmstadt, Gary L.; Saha, Senjuti; Islam, Maksuda; Chowdhury, Atique I.; Foster, Dona; Naheed, Aliya; Arifeen, Shams El; Baqui, Abdullah H.; Qazi, Shamim A.; Luby, Stephen P.; Breiman, Robert F.; Santosham, Mathuram; Black, Robert E.; Crook, Derrick W.

    2012-01-01

    Background Streptococcus pneumoniae is a leading cause of meningitis in countries where pneumococcal conjugate vaccines (PCV) targeting commonly occurring serotypes are not routinely used. However, effectiveness of PCV would be jeopardized by emergence of invasive pneumococcal diseases (IPD) caused by serotypes which are not included in PCV. Systematic hospital based surveillance in Bangladesh was established and progressively improved to determine the pathogens causing childhood sepsis and meningitis. This also provided the foundation for determining the spectrum of serotypes causing IPD. This article reports an unprecedented upsurge of serotype 2, an uncommon pneumococcal serotype, without any known intervention. Methods and Findings Cases with suspected IPD had blood or cerebrospinal fluid (CSF) collected from the beginning of 2001 till 2009. Pneumococcal serotypes were determined by capsular swelling of isolates or PCR of culture-negative CSF specimens. Multicenter national surveillance, expanded from 2004, identified 45,437 patients with suspected bacteremia who were blood cultured and 10,618 suspected meningitis cases who had a lumber puncture. Pneumococcus accounted for 230 culture positive cases of meningitis in children <5 years. Serotype-2 was the leading cause of pneumococcal meningitis, accounting for 20.4% (45/221; 95% CI 15%–26%) of cases. Ninety eight percent (45/46) of these serotype-2 strains were isolated from meningitis cases, yielding the highest serotype-specific odds ratio for meningitis (29.6; 95% CI 3.4–256.3). The serotype-2 strains had three closely related pulsed field gel electrophoresis types. Conclusions S. pneumoniae serotype-2 was found to possess an unusually high potential for causing meningitis and was the leading serotype-specific cause of childhood meningitis in Bangladesh over the past decade. Persisting disease occurrence or progressive spread would represent a major potential infection threat since serotype-2 is not included in PCVs currently licensed or under development. PMID:22479314

  14. [Pneumococcal meningitis in a pregnant woman].

    PubMed

    Scharek, Petra; Jekkel, Csilla; Budai, József; Szilasi, Zsuzsanna; Helferich, Frigyes; Arva, Ilona; Váradi, András; Létay, Erzsébet; Katona, Katalin; Rókusz, László

    2014-01-30

    Bacterial meningitis is a life-threatening disease. The incidence of meningitis is about 2.6-6 cases per 100.000 adults per year in developed countries. The most common causative microorganisms are Sreptococcus pneumoniae and Neisseria meningitidis. A 33-year-old multigravida, at 24 week of gestation was admitted to the hospital because of ear pain, haedache, fever and confusion. Lumbal puncture was performed and cerebrospinal fluid analysis showed signs of bacterial meningitis. Latex agglutination test was positive for S. pneumoniae, Gram-positive diplococci have seen under microscope and later cultivation verified S. pneumoniae as the causative agent. After ceftriaxon, dexamethasone administration and treatment in intensive care unit, left side mastoidectomy was performed since cranial computed tomography showed acut exacerbation of chronic mastoiditis on the left side. After extubation, mobilisation and 14 days antibiotic treatment the patient, who had residual hearing loss on the left side, was discharged from the hospital. During the treatment the foetal parameters were normal. The patient at 39 week of gestation gave birth to a healthy infant. Forty-eight case reports have been published in this topic around the world until April, 2012. The most common causative agents were S. pneumoniae and Listeria monocytogenes. Because of the little amount of data, it is hard to appreciate the actual incidence and prognosis of this life-threatening illness both for mother and infant. As far as we know this is the first published case report of meningitis during pregnancy in Hungary. By this article we would like to draw attention to the importance of teamwork, of prevention of brain abscess formation and of the removal of the infection's focus. PMID:24654448

  15. Neopterin Is a Cerebrospinal Fluid Marker for Treatment Outcome Evaluation in Patients Affected by Trypanosoma brucei gambiense Sleeping Sickness

    PubMed Central

    Tiberti, Natalia; Lejon, Veerle; Hainard, Alexandre; Courtioux, Bertrand; Robin, Xavier; Turck, Natacha; Kristensson, Krister; Matovu, Enock; Enyaru, John Charles; Mumba Ngoyi, Dieudonné; Krishna, Sanjeev; Bisser, Sylvie; Ndung?u, Joseph Mathu; Büscher, Philippe; Sanchez, Jean-Charles

    2013-01-01

    Background Post-therapeutic follow-up is essential to confirm cure and to detect early treatment failures in patients affected by sleeping sickness (HAT). Current methods, based on finding of parasites in blood and cerebrospinal fluid (CSF) and counting of white blood cells (WBC) in CSF, are imperfect. New markers for treatment outcome evaluation are needed. We hypothesized that alternative CSF markers, able to diagnose the meningo-encephalitic stage of the disease, could also be useful for the evaluation of treatment outcome. Methodology/Principal findings Cerebrospinal fluid from patients affected by Trypanosoma brucei gambiense HAT and followed for two years after treatment was investigated. The population comprised stage 2 (S2) patients either cured or experiencing treatment failure during the follow-up. IgM, neopterin, B2MG, MMP-9, ICAM-1, VCAM-1, CXCL10 and CXCL13 were first screened on a small number of HAT patients (n?=?97). Neopterin and CXCL13 showed the highest accuracy in discriminating between S2 cured and S2 relapsed patients (AUC 99% and 94%, respectively). When verified on a larger cohort (n?=?242), neopterin resulted to be the most efficient predictor of outcome. High levels of this molecule before treatment were already associated with an increased risk of treatment failure. At six months after treatment, neopterin discriminated between cured and relapsed S2 patients with 87% specificity and 92% sensitivity, showing a higher accuracy than white blood cell numbers. Conclusions/Significance In the present study, neopterin was highlighted as a useful marker for the evaluation of the post-therapeutic outcome in patients suffering from sleeping sickness. Detectable levels of this marker in the CSF have the potential to shorten the follow-up for HAT patients to six months after the end of the treatment. PMID:23469311

  16. Cerebrospinal Fluid Abnormalities in HIV-Negative Patients with Secondary and Early Latent Syphilis and Serum VDRL ? 1:32

    PubMed Central

    Pastuszczak, Maciej; Zeman, Jacek; Jaworek, Andrzej K; Wojas-Pelc, Anna

    2013-01-01

    Background: Syphilis is caused by a spirochete Treponema pallidum. Invasion of the central nervous system (CNS) by T. pallidum may appear early during the course of disease. The diagnosis of confirmed neurosyphilis is based on the reactive Venereal Disease Research Laboratory (VDRL) in cerebrospinal fluid (CSF). Recent studies indicated that serum RPR ? 1:32 are associated with higher risk of reactivity of CSF VDRL. Aims: The main aim of the current study was to assess cerebrospinal fluid serological and biochemical abnormalities in HIV negative subjects with secondary and early latent syphilis and serum VDRL ? 1:32. Materials and Methods: Clinical and laboratory data of 33 HIV-negative patients with secondary and early latent syphilis, with the serum VDRL titer ? 1:32, who underwent a lumbar puncture and were treated in Department of Dermatology at Jagiellonian University School of Medicine in Cracow, were collected. Results: Clinical examination revealed no symptoms of CNS involvement in all patients. 18% (n = 6) of patients met the criteria of confirmed neurosyphilis (reactive CSF-VDRL). In 14 (42%) patients CSF WBC count ? 5/ul was found, and in 13 (39%) subjects there was elevated CSF protein concentration (? 45 mg/dL). 10 patients had CSF WBC count ? 5/ul and/or elevated CSF protein concentration (? 45 mg/dL) but CSF-VDRL was not reactive. Conclusions: Indications for CSF examination in HIV-negative patients with early syphilis are the subject of discussion. It seems that all patients with syphilis and with CSF abnormalities (reactive serological tests, elevated CSF WBC count, elevated protein concentration) should be treated according to protocols for neurosyphilis. But there is a need for identification of biomarkes in order to identify a group of patients with syphilis, in whom risk of such abnormalities is high. PMID:23919017

  17. Cerebrospinal fluid levels of inflammation, oxidative stress and NAD+ are linked to differences in plasma carotenoid concentrations

    PubMed Central

    2014-01-01

    Background The consumption of foods rich in carotenoids that possess significant antioxidant and inflammatory modulating properties has been linked to reduced risk of neuropathology. The objective of this study was to evaluate the relationship between plasma carotenoid concentrations and plasma and cerebrospinal fluid (CSF) markers of inflammation, oxidative stress and nicotinamide adenine dinucleotide (NAD+) in an essentially healthy human cohort. Methods Thirty-eight matched CSF and plasma samples were collected from consenting participants who required a spinal tap for the administration of anaesthetic. Plasma concentrations of carotenoids and both plasma and cerebrospinal fluid (CSF) levels of NAD(H) and markers of inflammation (IL-6, TNF-?) and oxidative stress (F2-isoprostanes, 8-OHdG and total antioxidant capacity) were quantified. Results The average age of participants was 53 years (SD?=?20, interquartile range?=?38). Both ?-carotene (P?=?0.01) and ?-carotene (P?

  18. Cerebrospinal-fluid-derived immunoglobulin G of different multiple sclerosis patients shares mutated sequences in complementarity determining regions.

    PubMed

    Singh, Vaibhav; Stoop, Marcel P; Stingl, Christoph; Luitwieler, Ronald L; Dekker, Lennard J; van Duijn, Martijn M; Kreft, Karim L; Luider, Theo M; Hintzen, Rogier Q

    2013-12-01

    B lymphocytes play a pivotal role in multiple sclerosis pathology, possibly via both antibody-dependent and -independent pathways. Intrathecal immunoglobulin G in multiple sclerosis is produced by clonally expanded B-cell populations. Recent studies indicate that the complementarity determining regions of immunoglobulins specific for certain antigens are frequently shared between different individuals. In this study, our main objective was to identify specific proteomic profiles of mutated complementarity determining regions of immunoglobulin G present in multiple sclerosis patients but absent in healthy controls. To achieve this objective, we purified immunoglobulin G from the cerebrospinal fluid of 29 multiple sclerosis patients and 30 healthy controls and separated the corresponding heavy and light chains via SDS-PAGE. Subsequently, bands were excised, trypsinized, and measured with high-resolution mass spectrometry. We sequenced 841 heavy and 771 light chain variable region peptides. We observed 24 heavy and 26 light chain complementarity determining regions that were solely present in a number of multiple sclerosis patients. Using stringent criteria for the identification of common peptides, we found five complementarity determining regions shared in three or more patients and not in controls. Interestingly, one complementarity determining region with a single mutation was found in six patients. Additionally, one other patient carrying a similar complementarity determining region with another mutation was observed. In addition, we found a skew in the ?-to-? ratio and in the usage of certain variable heavy regions that was previously observed at the transcriptome level. At the protein level, cerebrospinal fluid immunoglobulin G shares common characteristics in the antigen binding region among different multiple sclerosis patients. The indication of a shared fingerprint may indicate common antigens for B-cell activation. PMID:23970564

  19. Cerebrospinal-fluid-derived Immunoglobulin G of Different Multiple Sclerosis Patients Shares Mutated Sequences in Complementarity Determining Regions*

    PubMed Central

    Singh, Vaibhav; Stoop, Marcel P.; Stingl, Christoph; Luitwieler, Ronald L.; Dekker, Lennard J.; van Duijn, Martijn M.; Kreft, Karim L.; Luider, Theo M.; Hintzen, Rogier Q.

    2013-01-01

    B lymphocytes play a pivotal role in multiple sclerosis pathology, possibly via both antibody-dependent and -independent pathways. Intrathecal immunoglobulin G in multiple sclerosis is produced by clonally expanded B-cell populations. Recent studies indicate that the complementarity determining regions of immunoglobulins specific for certain antigens are frequently shared between different individuals. In this study, our main objective was to identify specific proteomic profiles of mutated complementarity determining regions of immunoglobulin G present in multiple sclerosis patients but absent in healthy controls. To achieve this objective, we purified immunoglobulin G from the cerebrospinal fluid of 29 multiple sclerosis patients and 30 healthy controls and separated the corresponding heavy and light chains via SDS-PAGE. Subsequently, bands were excised, trypsinized, and measured with high-resolution mass spectrometry. We sequenced 841 heavy and 771 light chain variable region peptides. We observed 24 heavy and 26 light chain complementarity determining regions that were solely present in a number of multiple sclerosis patients. Using stringent criteria for the identification of common peptides, we found five complementarity determining regions shared in three or more patients and not in controls. Interestingly, one complementarity determining region with a single mutation was found in six patients. Additionally, one other patient carrying a similar complementarity determining region with another mutation was observed. In addition, we found a skew in the ?-to-? ratio and in the usage of certain variable heavy regions that was previously observed at the transcriptome level. At the protein level, cerebrospinal fluid immunoglobulin G shares common characteristics in the antigen binding region among different multiple sclerosis patients. The indication of a shared fingerprint may indicate common antigens for B-cell activation. PMID:23970564

  20. Toscana virus meningitis in Portugal, 2002-2005.

    PubMed

    Santos, L; Simões, J; Costa, R; Martins, S; Lecour, H

    2007-06-01

    Toscana virus infection is endemic in Italy, but has also been documented in other Mediterranean countries. Our aim was to investigate the occurrence of Toscana virus (TOSV) meningitis in children and young adults in a metropolitan area in the north of Portugal. Cerebrospinal fluid samples from 308 patients with the diagnosis of meningitis and with negative bacterial culture were tested for enteroviruses and herpesviruseses by reverse transcription PCR. Those samples that proved negative for enterovirus and herpesvirus were tested for Toscana virus with a commercial reverse transcription nested PCR assay. In total, we investigated 106 samples, collected between May and September during the four-year period between 2002 and 2005 from patients younger than 30 years old. Toscana virus was the cause of meningitis in six (5.6%) of the cases, three children and three young adults. All had a benign course and self-limited disease. Since a first case report of TOSV infection 1985 and another in 1996, both in foreign tourists, these six cases of Toscana virus meningitis are, to our knowledge, the first diagnosed in Portuguese inhabitants, and they underline the need for more studies on the prevalence of this virus in Portugal. PMID:17991401